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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">As doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o &#40;CDG&#41; s&#227;o doen&#231;as gen&#233;ticas da s&#237;ntese e processamentos dos glicanos das glicoprote&#237;nas e glicolip&#237;dios&#44; de heran&#231;a autoss&#244;mica recessiva em sua maioria&#44; caracterizadas pela defici&#234;ncia total ou parcial de prote&#237;nas envolvidas na glicosila&#231;&#227;o de prote&#237;nas ou lip&#237;dios&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">H&#225; dois tipos principais de glicosila&#231;&#227;o de prote&#237;nas&#58; N&#8208;glicosila&#231;&#227;o e O&#8208; glicosila&#231;&#227;o&#46; A N&#8208;glicosila&#231;&#227;o &#40;liga&#231;&#227;o de N&#8208;glicanos ao grupo amino de asparaginas&#41; compreende uma etapa de montagem e uma etapa de processamento que se estende por tr&#234;s compartimentos&#58; citoplasma&#44; ret&#237;culo endoplasm&#225;tico e complexo de Golgi&#46; A O&#8208;glicosila&#231;&#227;o &#40;liga&#231;&#227;o de O&#8208;glicanos a grupos hidroxila de treoninas ou serinas&#41; n&#227;o apresenta etapa de processamento e consiste apenas na etapa de montagem&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> Dessa forma&#44; existem CDG que envolvem N&#8208;glicosila&#231;&#227;o somente&#44; O&#8208;glicosila&#231;&#227;o somente ou ambas&#46; Estima&#8208;se que 94&#37; dos indiv&#237;duos com CDG apresentem defeitos de N&#8208;glicosila&#231;&#227;o&#44; os mais frequentes s&#227;o a PMM2&#8208;CDG &#40;antiga CDG Ia&#41; e a ALG6&#8208;CDG &#40;antiga CDG Ic&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Desde a primeira descri&#231;&#227;o cl&#237;nica em 1980&#44; mais de 100 tipos de CDG foram identificados &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> As manifesta&#231;&#245;es cl&#237;nicas podem aparecer ainda na gesta&#231;&#227;o&#44; como a hidropisia fetal n&#227;o imune&#44; microcefalia&#44; malforma&#231;&#245;es cong&#234;nitas e dismorfias faciais&#59; em neonatos e na inf&#226;ncia&#44; podem ser encontrados hipoplasia cerebelar&#44; mamilos invertidos&#44; estrabismo&#44; movimentos oculares anormais&#44; retardo de desenvolvimento neuropsicomotor &#40;RDNPM&#41;&#44; hipotonia&#44; ataxia&#44; hiporreflexia&#44; convuls&#245;es&#44; anorexia&#44; v&#244;mitos&#44; diarreia&#44; defeitos do sistema imunol&#243;gico&#44; hipogonadismo&#44; lipodistrofia&#44; hepatomegalia&#44; cifose&#44; escoliose e cardiomiopatia&#46; Podem tamb&#233;m ocorrer fen&#243;tipos mais leves&#44; sem dismorfias e com RNDPM leve&#46; Recomenda&#8208;se&#44; portanto&#44; que a hip&#243;tese de CDG seja considerada em qualquer caso de s&#237;ndrome inexplicada&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao diagn&#243;stico&#44; a isoeletrofocaliza&#231;&#227;o de transferrina &#40;IEFTF&#41; &#233; um teste de triagem para CDGs que envolvem N&#8208;glicosila&#231;&#227;o&#44; pois a transferrina &#233; N&#8208;glicosilada&#46; A IEFTF&#44; nesses casos&#44; mostra um deslocamento cat&#243;dico como consequ&#234;ncia da defici&#234;ncia parcial de &#225;cido si&#225;lico&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A t&#233;cnica detecta dois padr&#245;es de altera&#231;&#227;o&#44; padr&#227;o de altera&#231;&#227;o do tipo 1&#44; associado principalmente a defeitos relacionados ao ret&#237;culo endoplasm&#225;tico &#40;antigamente denominados CDG do tipo I&#41;&#44; e o padr&#227;o do tipo 2&#44; associado&#44; por sua vez&#44; a defeitos relacionados ao sistema Golgi &#40;antigamente denominados CDG do tipo II&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">No Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Rio Grande do Sul &#40;RS&#41;&#44; Brasil &#40;LEIM&#8208;HCPA&#41;&#44; a IEFTF &#233; o &#250;nico exame feito para investiga&#231;&#227;o de CDG&#46; O m&#233;todo usado foi adaptado daquele descrito em 1995 por Hackler&#44; Rolf &#38; Kleine&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Os casos alterados da IEFTF&#44; ou com suspeita de defeitos de O&#8208;glicosila&#231;&#227;o&#44; devem seguir a investiga&#231;&#227;o para fins de confirma&#231;&#227;o diagn&#243;stica&#44; seja por ensaios enzim&#225;ticos&#44; an&#225;lises de espectrometria de massa &#40;ESI&#47;MS&#44; MALDI&#8208;TOF&#41; ou an&#225;lise gen&#233;tica&#46; Frisa&#8208;se que v&#225;rias condi&#231;&#245;es al&#233;m de CDG est&#227;o associadas a resultados alterados na IEFTF&#44; como galactosemia&#44; intoler&#226;ncia heredit&#225;ria &#224; frutose&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;8</span></a> hepatopatias&#44; uso cr&#244;nico e abusivo de &#225;lcool&#44; infec&#231;&#245;es por microrganismos produtores de neuraminidase e polimorfismos da transferrina&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#8211;12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">No Brasil&#44; pouco se sabe sobre a preval&#234;ncia ou incid&#234;ncia de CDG na popula&#231;&#227;o&#44; bem como sobre a disponibilidade dos exames tanto para a triagem como para o diagn&#243;stico dessa doen&#231;a&#46; O objetivo deste estudo foi caracterizar os casos triados pelo exame de IEFTF&#44; de 2008 a 2017&#44; no LEIM&#8208;HCPA&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Metodologia</span><p id="par0045" class="elsevierStylePara elsevierViewall">Estudo observacional e retrospectivo de indiv&#237;duos investigados por IEFTF no LEIM&#8208;HCPA&#44; de 2008 a 2017&#46; Em 2018&#44; foram coletadas e analisadas informa&#231;&#245;es de fichas laboratoriais dos mesmos&#46; O presente estudo foi aprovado pelo comit&#234; de &#233;tica do HCPA com o n&#250;mero 18&#8208;0324&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Coleta de dados</span><p id="par0050" class="elsevierStylePara elsevierViewall">A coleta de dados ocorreu por meio de revis&#227;o das fichas do LEIM&#8208;HCPA&#46; Os seguintes dados foram considerados&#58; data da feitura da IEFTF&#44; idade do indiv&#237;duo no momento&#44; sexo&#44; local de origem&#44; resultado obtido na IEFTF&#44; sinais e sintomas e informa&#231;&#245;es de hist&#243;rico familiar&#46; Al&#233;m disso&#44; para os casos de IEFTF alterados&#44; se houve confirma&#231;&#227;o do diagn&#243;stico de CDG ou de outra doen&#231;a mediante exames complementares&#46; Para os indiv&#237;duos provenientes do HCPA&#44; tamb&#233;m foi feita uma revis&#227;o de prontu&#225;rio eletr&#244;nico dos indiv&#237;duos com resultados alterados&#46; Foram consideradas como n&#227;o existentes as informa&#231;&#245;es pertinentes a este estudo que n&#227;o constavam na ficha laboratorial ou no prontu&#225;rio eletr&#244;nico dos indiv&#237;duos&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise estat&#237;stica</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os bancos de dados foram constru&#237;dos em Microsoft Office Excel 2010 e para a an&#225;lise estat&#237;stica foi usado o programa IBM SPSS Statistics 18&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Os aspectos descritivos foram apresentados nas formas de frequ&#234;ncias para os dados correspondentes &#224; IEFTF nos padr&#245;es normal e alterado&#46; M&#233;dias&#44; desvios&#8208;padr&#227;o&#44; medianas e quartis foram usados para os dados de idade&#46; Para a compara&#231;&#227;o das vari&#225;veis entre os grupos com e sem altera&#231;&#227;o na IEFTF&#44; usou&#8208;se&#44; inicialmente&#44; teste exato de qui&#8208;quadrado de Person&#44; com corre&#231;&#227;o de continuidade&#44; ou exato de Fisher &#40;signific&#226;ncia&#58; p &#60; 0&#44;05&#41;&#46; Posteriormente&#44; foram feitas an&#225;lises residuais &#40;raz&#227;o de preval&#234;ncia bruta e raz&#227;o de preval&#234;ncia ajustada &#8208; regress&#227;o de Poisson com vari&#226;ncia robusta&#41; nos casos com p &#60; 0&#44;05 na an&#225;lise anterior&#46; Foram consideradas como diferindo entre os grupos com IEFTF alterada ou normal somente as vari&#225;veis que apresentaram raz&#227;o de preval&#234;ncia ajustada significativa&#46; Para a an&#225;lise da idade de feitura do teste&#44; foi usado o teste n&#227;o param&#233;trico de Mann&#8208;Whitney&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="par0065" class="elsevierStylePara elsevierViewall">De 2008 a 2017&#44; 1&#46;546 indiv&#237;duos fizeram a IEFTF&#44; 566 &#40;37&#37;&#41; provenientes do RS e 980 &#40;63&#37;&#41; de outros estados do Brasil &#91;Santa Catarina&#47;Paran&#225;&#58; 62 &#40;4&#37;&#41;&#59; Regi&#227;o Sudeste 744 &#40;48&#37;&#41;&#59; Nordeste 77 &#40;5&#37;&#41;&#59; Centro&#8208;Oeste 64 &#40;4&#37;&#41;&#59; Norte 33 &#40;2&#37;&#41;&#93;&#46; A m&#233;dia anual do n&#250;mero de casos investigados foi de 156 &#177; 49&#47;casos por ano e&#44; desses&#44; 5 &#177; 2&#44;8 casos&#47;ano com IEFTF alterada&#46; O maior n&#250;mero de casos investigados foi em 2012 &#40;246&#41; e em 2017 o maior n&#250;mero de casos alterados &#40;11&#41;&#46; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Dos indiv&#237;duos&#44; 51 &#40;3&#37;&#59; RS &#61; 23&#41; apresentaram altera&#231;&#227;o no exame IEFTF&#46; Desses&#44; 14 &#40;28&#37;&#41; tiveram a investiga&#231;&#227;o conclu&#237;da &#40;RS &#61; 11&#41;&#44; quatro &#40;RS &#61; 3&#41; chegaram ao diagn&#243;stico confirmat&#243;rio de CDG por an&#225;lise gen&#233;tica &#40;MPDU1&#8208;CDG &#61; 1&#44; SLC35A2&#8208;CDG &#61; 1&#44; PMM2&#8208;CDG &#61; 2&#41;&#46; Para os casos restantes&#44; exames complementares permitiram a exclus&#227;o de CDG e o diagn&#243;stico confirmat&#243;rio de outras doen&#231;as&#58; galactosemia cl&#225;ssica &#40;n &#61; 4&#44; todos confirmados por meio da medida da atividade da Gal1PUT&#41;&#44; intoler&#226;ncia heredit&#225;ria &#224; frutose &#40;n &#61; 4&#44; todos confirmados por an&#225;lise gen&#233;tica&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41; e dois casos de doen&#231;a peroxissomal &#40;ambos confirmados por medida de &#225;cidos graxos de cadeia muito longa&#41;&#46; Para os 37 casos restantes&#44; n&#227;o foi poss&#237;vel a obten&#231;&#227;o de informa&#231;&#245;es adicionais acerca da conclus&#227;o diagn&#243;stica&#46; Considerando apenas os casos do RS&#44; dos 566 casos investigados por IEFTF&#44; 23 apresentaram padr&#227;o alterado &#40;4&#37;&#41; e 11&#47;23 &#40;48&#37;&#41; tiveram o diagn&#243;stico de alguma doen&#231;a confirmado &#40;CDG &#61; 3&#47;11 ou 27&#37;&#41;&#46; A <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a> apresenta o perfil completo dos indiv&#237;duos inclu&#237;dos no estudo&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">A faixa de 11 a 36 meses foi a que apresentou a maior preval&#234;ncia de resultados alterados&#44; 48&#37; dos indiv&#237;duos que apresentaram resultado alterado encontram&#8208;se nessa faixa et&#225;ria&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A manifesta&#231;&#227;o cl&#237;nica mais comum nos casos investigados foi RDNPM&#44; seguido de convuls&#245;es&#44; hipotonia&#44; defici&#234;ncia intelectual e dismorfias&#46; Por&#233;m&#44; os sintomas mais frequentes nos casos com altera&#231;&#245;es na IEFTF foram&#58; RDNPM&#44; hipotonia&#44; hepatopatia&#44; defici&#234;ncia intelectual e hepatomegalia&#44; foram mamilos invertidos &#40;raz&#227;o de preval&#234;ncia ajustada &#61; 11&#41;&#44; seguidos de hepatopatia&#44; hipoglicemia&#44; altera&#231;&#245;es oftalmol&#243;gicas e recorr&#234;ncia familial &#224;s manifesta&#231;&#245;es cl&#237;nicas estatisticamente associadas &#224; IEFTF alterada &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discuss&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">CDGs t&#234;m sido descritas como um grande desafio diagn&#243;stico&#44; uma vez que&#44; nesse conjunto de doen&#231;as&#44; quase todos os &#243;rg&#227;os s&#227;o acometidos e uma grande variedade de sintomas j&#225; foi descrita&#46; Assim&#44; a recomenda&#231;&#227;o &#233; considerar CDG em qualquer caso de doen&#231;a n&#227;o explicada&#44; principalmente quando h&#225; presen&#231;a de sintomas neurol&#243;gicos&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> No Brasil&#44; um outro fator que contribui para a dificuldade diagn&#243;stica &#233; a dificuldade de acesso a exames confirmat&#243;rios&#46; Dentro desse contexto&#44; nossos dados sugerem que existe subdiagn&#243;stico de CDG no Brasil e que esfor&#231;os devem ser feitos para a implanta&#231;&#227;o dos testes diagn&#243;sticos&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O protocolo de investiga&#231;&#227;o para CDG estabelecido no HCPA n&#227;o contempla uma investiga&#231;&#227;o completa para a doen&#231;a&#44; uma vez que somente a IEFTF &#233; oferecida&#46; O protocolo mais custo&#8208;efetivo&#44; ap&#243;s terem sido descartadas outras doen&#231;as que possam causar altera&#231;&#227;o da IEFTF&#44; n&#227;o est&#225; bem estabelecido&#46; Uma estrat&#233;gia poss&#237;vel seria o sequenciamento inicial apenas do gene <span class="elsevierStyleItalic">PMM2</span> para os casos alterados com padr&#227;o de CDG tipo I&#44; uma vez que esses s&#227;o os casos mais frequentes de CDG&#46; Se o sequenciamento n&#227;o evidenciar anormalidade&#44; uma an&#225;lise de painel com genes espec&#237;ficos para CDG e&#44; em caso de resultado negativo&#44; o sequenciamento completo do exoma estariam indicados&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> Outra estrat&#233;gia poss&#237;vel seria a investiga&#231;&#227;o inicial direta por meio de painel inclu&#237;dos os genes causadores de CDG&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Apesar de as CDG serem doen&#231;as gen&#233;ticas raras&#44; existe um n&#250;mero significativo de indiv&#237;duos com suspeita da doen&#231;a&#44; como pode ser visto pela m&#233;dia anual de casos investigados por IEFTF no LEIM&#8208;HCPA&#46; Entretanto&#44; o n&#250;mero de casos confirmados foi pequeno &#40;apenas 4 indiv&#237;duos em dez anos&#41;&#44; o que sugere a ocorr&#234;ncia de um subdiagn&#243;stico dessas doen&#231;as em nosso pa&#237;s&#44; ainda mais considerando que a frequ&#234;ncia estimada para PMM2&#8208;CDG&#44; que vem ser a CDG mais comum&#44; &#233; de cerca de 1&#47;20&#46;000 rec&#233;m&#8208;nascidos&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> Mesmo na aus&#234;ncia de tratamento espec&#237;fico para a maioria das CDG&#44; a confirma&#231;&#227;o do seu diagn&#243;stico &#233; fundamental para o aconselhamento gen&#233;tico&#44; haja vista o elevado risco de recorr&#234;ncia &#40;a maioria das CDG apresenta padr&#227;o de heran&#231;a autoss&#244;mico recessivo ou ligado ao X&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Nosso estudo mostrou&#44; tamb&#233;m&#44; que galactosemia cl&#225;ssica e intoler&#226;ncia heredit&#225;ria &#224; frutose s&#227;o causas frequentes de altera&#231;&#245;es na IEFTF&#46; Galactosemia tem sido referida como um segundo tipo de defeito de glicosila&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;7</span></a> A literatura aponta que h&#225; anormalidades na glicosila&#231;&#227;o de N&#8208;glicanos na transferrina s&#233;rica em neonatos com galactosemia n&#227;o tratados&#46; Essas anormalidades&#44; em sua grande parte&#44; s&#227;o resolvidas com o tratamento diet&#233;tico com restri&#231;&#227;o de galactose&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;15&#44;16</span></a> Outra doen&#231;a que pode acarretar em hipoglicosila&#231;&#227;o das isoformas de transferrina &#233; a intoler&#226;ncia heredit&#225;ria &#224; frutose&#46; &#201; causada por uma defici&#234;ncia na atividade da enzima aldolase B&#59; consequentemente&#44; a frutose&#8208;1P &#233; acumulada em c&#233;lulas hep&#225;ticas&#44; acarreta a inibi&#231;&#227;o da atividade da fosfomanose isomerase&#44; enzima presente nas primeiras etapas da glicosila&#231;&#227;o de prote&#237;nas&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Por outro lado&#44; tendo&#8208;se em considera&#231;&#227;o que o f&#237;gado &#233; um dos principais &#243;rg&#227;os de glicosila&#231;&#227;o&#44; tamb&#233;m respons&#225;vel pela produ&#231;&#227;o da maioria das prote&#237;nas s&#233;ricas glicosiladas&#44; defeitos de glicosila&#231;&#227;o est&#227;o associados a sintomas cl&#237;nicos hep&#225;ticos&#44; os quais est&#227;o presentes em torno de 20&#37; dos casos de CDG&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Nosso estudo corrobora esses achados&#44; visto que as hepatopatias apresentam forte associa&#231;&#227;o com altera&#231;&#245;es no padr&#227;o da IEFTF &#40;indiv&#237;duos com hepatopatia t&#234;m 4&#44;6 vezes mais chances de apresentar uma altera&#231;&#227;o na IEFTF do que indiv&#237;duos sem esse sintoma&#41;&#46; Hepatopatias est&#227;o associadas a resultados alterados na IEFTF&#44; por&#233;m essa altera&#231;&#227;o pode n&#227;o estar diretamente associada &#224;s CDG&#44; e sim a outros EIM que afetam o f&#237;gado&#44; como as doen&#231;as peroxissomais&#44; identificadas em dois casos com altera&#231;&#227;o da IEFTF no nosso estudo&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">O fato de que faixa de 11 a 36 meses foi a que apresentou a maior preval&#234;ncia de resultados alterados da IEFTF sugere que as condi&#231;&#245;es causadoras de altera&#231;&#245;es na IEFTF &#40;entre elas&#44; as CDG&#41; apresentam&#8208;se principalmente na inf&#226;ncia&#44; ap&#243;s o per&#237;odo de lact&#226;ncia&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nossos dados mostram que a presen&#231;a de mamilos invertidos apresentou o maior &#237;ndice de associa&#231;&#227;o com a altera&#231;&#227;o da IEFTF &#40;a raz&#227;o de preval&#234;ncia ajustada demonstra que esse sintoma aumenta em 11 vezes a chance de o indiv&#237;duo apresentar a IEFTF alterada&#41;&#46; Mamilos invertidos est&#227;o geralmente presentes em indiv&#237;duos com CDG ao nascimento&#44; podem voltar &#224; posi&#231;&#227;o normal em poucos dias ou semanas de vida&#46; Entretanto&#44; a persist&#234;ncia do achado na vida adulta pode ocorrer&#46; &#201; importante salientar&#44; no entanto&#44; que a lista de s&#237;ndromes associadas a mamilos invertidos &#233; extensa&#44; inclui&#44; por exemplo&#44; s&#237;ndromes de Turner&#44; de Smith&#8208;Lemli&#8208;Optiz e de Robinow&#44; entre outras&#44; por&#233;m&#44; tamb&#233;m pode ser observado em indiv&#237;duos normais&#46; No caso das CDG&#44; os mamilos invertidos s&#227;o encontrados com maior frequ&#234;ncia em indiv&#237;duos com defeitos de N&#8208;glicosila&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o &#224;s limita&#231;&#245;es do estudo&#44; &#233; importante mencionar que est&#225; baseado em informa&#231;&#245;es cl&#237;nicas presentes nos prontu&#225;rios dos indiv&#237;duos com suspeita de CDG&#46; Outra limita&#231;&#227;o importante&#44; com rela&#231;&#227;o aos indiv&#237;duos provenientes de outras regi&#245;es do pa&#237;s&#44; &#233; que&#44; ap&#243;s a libera&#231;&#227;o do laudo aos servi&#231;os de origem do paciente&#44; n&#227;o temos informa&#231;&#245;es do seguimento que esses indiv&#237;duos tiveram&#44; ou seja&#44; se o paciente concluiu a investiga&#231;&#227;o ou n&#227;o&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclus&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">Apesar das limita&#231;&#245;es do estudo no que diz respeito &#224; an&#225;lise retrospectiva dos casos&#44; mediante revis&#227;o de prontu&#225;rios e a falta de uniformiza&#231;&#227;o do atendimento e diagn&#243;stico dos pacientes provenientes de diferentes regi&#245;es do pa&#237;s&#44; verificou&#8208;se que h&#225; necessidade da implanta&#231;&#227;o de novas t&#233;cnicas para diagn&#243;stico de CDG e o estabelecimento de um protocolo mais completo para a investiga&#231;&#227;o das CDG no LEIM&#8208;HCPA&#46; Os achados mostram que&#44; apesar de altera&#231;&#245;es na IEFTF terem sido reportadas em 51 casos&#44; conseguimos constatar em apenas quatro indiv&#237;duos o diagn&#243;stico confirmado para CDG&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Os dados obtidos tamb&#233;m mostram que os principais sintomas que levaram &#224; suspeita de CDG foram neurol&#243;gicos&#46; No entanto&#44; os indiv&#237;duos que apresentarem mamilos invertidos&#44; hepatopatia&#44; hipoglicemia&#44; altera&#231;&#245;es oftalmol&#243;gicas e a presen&#231;a de outros casos na fam&#237;lia foram os que tiveram maior probabilidade de ter IEFTF alterada&#46; Dessa forma&#44; a triagem para CDG deve ser especialmente considerada quando houver a presen&#231;a dessas manifesta&#231;&#245;es cl&#237;nicas&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Financiamento</span><p id="par0130" class="elsevierStylePara elsevierViewall">Fundo de Incentivo &#224; Pesquisa e Eventos do Hospital de Cl&#237;nicas de Porto Alegre &#40;FIPE&#8208;HCPA&#41;&#44; n&#250;mero do financiamento&#58; 18&#8208;0324&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflitos de interesse</span><p id="par0135" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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    "fechaRecibido" => "2019-02-18"
    "fechaAceptado" => "2019-05-14"
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          "palabras" => array:4 [
            0 => "Isoeletrofocaliza&#231;&#227;o"
            1 => "Transferrina"
            2 => "Doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To characterize cases of suspected congenital disorders of glycosylation &#40;CDG&#41; investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Observational&#44; cross&#8208;sectional&#44; retrospective study&#46; The laboratory records of 1&#44;546 individuals &#40;median age &#61; 36 months&#44; 25&#8208;75 IQR &#61; 10&#8208;108&#59; males &#61; 810&#41; submitted to the TfIEF test during the period were reviewed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Fifty&#8208;one individuals &#40;3&#37;&#41; had an altered TfIEF pattern &#40;5 &#177; 2&#46;8 cases&#47;year&#59; median age &#61; 24 months&#44; 25&#8208;75 IQR &#61; 11&#8208;57 months&#59; males &#61; 27&#44; 53&#37;&#41;&#46; For 14 of them&#44; data on diagnosis conclusion were available &#40;classic galactosemia &#61; 4&#59; hereditary fructose intolerance &#61; 4&#59; peroxisomal diseases &#61; 2&#59; PMM2&#8208;CDG &#61; 2&#59; MPDU1&#8208;CDG &#61; 1&#59; SLC35A2&#8208;CDG &#61; 1&#41;&#46;Comparing the cases with the normal and altered TfIEF patterns&#44; there was a higher prevalence of altered cases in the age group from 11 months to 3 years&#46; There was an increase in the likelihood of change in TfIEF&#44; especially in the presence of inverted nipples or liver disease&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The data suggest that the investigation of a case with suspected CDG is a complex problem&#44; being aggravated by the existence of other IEMs &#40;inborn errors of metabolism&#41; associated with altered TfIEF pattern and lack of access to confirmatory tests&#46; The presence of inverted nipples and liver disease&#44; especially in individuals aged 11 months to 3 years&#44; should suggest the need for TfIEF investigation&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Caracterizar os casos com suspeita de CDG investigados em laborat&#243;rio do sul do Brasil pelo exame de IEFTF de 2008 a 2017&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodologia</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional&#44; transversal&#44; retrospectivo&#46; Foram revisadas as fichas laboratoriais de 1&#46;546 indiv&#237;duos &#40;mediana de idade &#61; 36 meses&#44; IQ 25&#8208;75 &#61; 10&#8208;108&#59; sexo masculino &#61; 810&#41; que fizeram o exame de IEFTF no per&#237;odo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cinquenta e um indiv&#237;duos &#40;3&#37;&#41; apresentaram padr&#227;o alterado na IEFTF &#40;5 &#177; 2&#44;8 casos&#47;ano&#59; mediana de idade &#61; 24 meses&#44; IQ 25&#8208;75 &#61; 11&#8208;57 meses&#59; sexo masculino &#61; 27&#44; 53&#37;&#41;&#46; Para 14 deles&#44; estavam dispon&#237;veis dados sobre a conclus&#227;o do diagn&#243;stico &#40;galactosemia cl&#225;ssica &#61; 4&#59; intoler&#226;ncia heredit&#225;ria &#224; frutose &#61; 4&#59; doen&#231;as peroxissomais &#61; 2&#59; PMM2&#8208;CDG &#61; 2&#59; MPDU1&#8208;CDG &#61; 1&#59; SLC35A2&#8208;CDG &#61; 1&#41;&#46; Comparando os casos com padr&#227;o normal e alterado na IEFTF&#44; houve maior preval&#234;ncia de casos alterados na faixa et&#225;ria de 11 meses a 3 anos&#46; Verificou&#8208;se um aumento na probabilidade de altera&#231;&#227;o na IEFTF principalmente na presen&#231;a de mamilos invertidos ou de hepatopatia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os nossos dados sugerem que a investiga&#231;&#227;o de um caso com suspeita de CDG &#233; complexa&#44; &#233; agravada pela exist&#234;ncia de outros EIM associados a padr&#227;o alterado na IEFTF e pela falta de acesso a exames confirmat&#243;rios&#46; A presen&#231;a principalmente de mamilos invertidos e de hepatopatia em indiv&#237;duos na faixa et&#225;ria de 11 meses a 3 anos deve sugerir a necessidade de investiga&#231;&#227;o por IEFTF&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Magalh&#227;es AP&#44; Burin MG&#44; Souza CF&#44; Bitencourt FH&#44; Sebasti&#227;o FM&#44; Silva TO&#44; et al&#46; Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation&#58; analysis of a ten&#8208;year experience in a Brazilian center&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#58;710&#8211;6&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Estudo feito na Universidade Federal do Rio Grande do Sul &#40;UFRGS&#41;&#44; Hospital de Cl&#237;nicas de Porto Alegre &#40;HCPA&#41;&#44; Porto Alegre&#44; RS&#44; Brasil&#46;</p>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero de casos que fizeram isoeletrofocaliza&#231;&#227;o da transferrina &#40;IETF&#41; por ano no Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Brasil&#46; Em destaque o n&#250;mero de casos alterados por ano e sua porcentagem&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ERGIC&#44; compartimento intermedi&#225;rio do ret&#237;culo endoplasm&#225;tico&#8208;Golgi&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Os tipos de CDG em negrito correspondem a casos diagnosticados na presente coorte&#46; A nomenclatura das CDG segue com o nome do gene onde ocorre a muta&#231;&#227;o hifenizado com CDG&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Fonte dos dados&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#8211;12</span></a></p>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC35D1&#8208;CDGPOGLUT1&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PIGA&#8208;CDGPIGC&#8208;CDGPIGG&#8208;CDGPIGL&#8208;CDGPIGM&#8208;CDGPIGN&#8208;CDGPIGO&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PIGQ&#8208;CDGPIGT&#8208;CDGPIGV&#8208;CDGPIGW&#8208;CDGPIGY&#8208;CDGPGAP1&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DOLK&#8208;CDGNUS1&#8208;CDGSRD5A3&#8208;CDGDPM1&#8208;CDGDPM2&#8208;CDGDPM3&#8208;CDG<span class="elsevierStyleBold">MPDU1&#8208;CDG</span>ATP6AP1&#8208;CDGTRAPPC11&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Golgi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MAN1B1&#8208;CDGMGAT2&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALT7&#8208;CDG XYLT1&#8208;CDGB3GALT6&#8208;CDG XYLT2&#8208;CDGB3GAT3&#8208;CDG GALNT3&#8208;CDGCHSY1&#8208;CDG LFNG&#8208;CDGEXT1&#8208;CDG POFUT1&#8208;CDGEXT2&#8208;CDGB3GALTL&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALNT1&#8208;CDGST3GAL5&#8208;CDGPGAP2&#8208;CDGPGAP3&#8208;CDG</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALT1&#8208;CDG COG4&#8208;CDGST3GAL3&#8208;CDG COG5&#8208;CDGSLC35A1&#8208;CDG COG6&#8208;CDG<span class="elsevierStyleBold">SLC35A2&#8208;CDG</span> COG7&#8208;CDGSLC35A3&#8208;CDG COG8&#8208;CDGSLC35C1&#8208;CDG ATP6V0A2&#8208;CDGCOG1&#8208;CDG TIMEM165&#8208;CDGCOG2&#8208;CD VPS138&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ERGIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SEC23B&#8208;CDGCCDC115&#8208;CDGTMEM199&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Membrana plasm&#225;tica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC39A8&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Membrana do sarcolema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B3GALNT2&#8208;CDGFKTN&#8208;CDGFKRP&#8208;CDGISPD&#8208;CDGLARGE&#8208;CDGPOMGNT1&#8208;CDGPOMT1&#8208;CDGPOMT2&#8208;CDGTMEM5&#8208;CDGPOMK&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2417624.png"
              ]
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Exemplos de doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o &#40;CDG&#41; descritas de acordo com sua localiza&#231;&#227;o celular e as diferentes vias de glicosila&#231;&#227;o</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AR&#44; autoss&#244;mica recessiva&#59; F&#44; feminino&#59; LX&#44; ligada ao X&#59; M&#44; masculino&#59; MG&#44; Minas Gerais&#59; Pac&#44; paciente&#59; RDNPM&#44; retardo do desenvolvimento neuropsicomotor&#59; RS&#44; Rio Grande do Sul&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pac&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Idade ao diagn&#243;stico &#40;meses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Origem&#40;Estado&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Consanguinidadeparental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Manifesta&#231;&#245;escl&#237;nicas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CDG &#40;heran&#231;a&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gen&#243;tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiomiopatia&#44; mamilos invertidos&#44; RDNPM&#44; dificuldades alimentares&#44; hipotonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PMM2&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;193G&#62;T&#47;422G&#62;A &#47; p&#46;Asp65Tyr&#47;Arg141His&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mamilos invertidos&#44; altera&#231;&#245;es esquel&#233;ticas&#44; RDNPM&#44; defici&#234;ncia intelectual&#44; altera&#231;&#245;es oftalmol&#243;gicas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PMM2&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;193G&#62;T&#47;422G&#62;A &#47; p&#46;Asp65Tyr&#47;Arg141His&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o dispon&#237;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MPDU1&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o dispon&#237;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dismorfias&#44; RDNPM&#44; convuls&#245;es&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">SLC35A2 &#8211; CDG &#40;LX&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;128T&#62;C &#40;p&#46;Leu43Pro&#41;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">IC&#44; intervalo de confian&#231;a&#59; IETFTF&#44; isoeletrofocaliza&#231;&#227;o da transferrina&#59; M&#44; sexo masculino&#59; NC&#44; n&#227;o calculado&#59; RDNPM&#44; retardo do desenvolvimento neuropsicomotor&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Compara&#231;&#227;o feita entre os casos com padr&#227;o normal e padr&#227;o alterado na IEFTF&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> 10 casos que n&#227;o tiveram o sexo do indiv&#237;duo informado&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Para as compara&#231;&#245;es&#44; inicialmente foi usado o teste do qui&#8208;quadrado de Person com corre&#231;&#227;o de continuidade&#44; ou o teste exato de Fisher &#40;<span class="elsevierStyleSup">c</span> resultados significativos&#44; p &#60; 0&#44;05&#41;&#59; ap&#243;s&#44; foi calculada a raz&#227;o de preval&#234;ncia bruta para as vari&#225;veis com p &#60; 0&#44;05 e&#44; para as vari&#225;veis com diferen&#231;as significativas na raz&#227;o de preval&#234;ncia bruta&#44; foi calculada a raz&#227;o de preval&#234;ncia ajustada&#46; As vari&#225;veis em negrito s&#227;o aquelas que apresentaram raz&#227;o de preval&#234;ncia ajusta estatisticamente significativa&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Manifesta&#231;&#245;es cl&#237;nicas&#40;n &#61; 1&#46;546indiv&#237;duos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IEFTFPadr&#227;o alterado&#40;n &#61; 51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IEFTFPadr&#227;o normal&#40;n &#61; 1&#46;495&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Raz&#227;o de preval&#234;ncia bruta&#40;IC&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Raz&#227;o de preval&#234;ncia ajustada&#40;IC&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Mediana de idade &#40;meses&#41; &#40;IQ 25 &#8211; 75&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;11 &#8208; 57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;10 &#8208; 108&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sexo masculino &#40;n &#61; 810&#47; 1536<span class="elsevierStyleSup">b</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;54&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">783 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RDNPM &#40;n &#61; 625&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">598 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Hipotonia &#40;n &#61; 326&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">307 &#40;20&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;3 &#40;1&#44;3 &#8208; 4&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5 &#40;0&#44;8 &#8208; 2&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Hepatopatias &#40;n &#61; 131&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">18 &#40;35&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">113 &#40;7&#44;5&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">6&#44;1 &#40;3&#44;5 &#8208; 10&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;6 &#40;2&#44;5 &#8208; 8&#44;7&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Defici&#234;ncia intelectual &#40;n &#61; 317&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">302 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatomegalia &#40;n &#61; 153&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139 &#40;9&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;5 &#40;1&#44;9 &#8208; 6&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;1 &#40;0&#44;5 &#8208; 2&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Altera&#231;&#245;es oftalmol&#243;gicas &#40;n &#61; 93&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">12 &#40;24&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">81 &#40;5&#44;4&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;9 &#40;2&#44;7 &#8208; 9&#44;1&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;8 &#40;1&#44;3 &#8208; 6&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Recorr&#234;ncia familial &#40;n &#61; 115&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">11 &#40;22&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">104 &#40;6&#44;9&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">3&#44;5 &#40;1&#44;8 &#8208; 6&#44;7&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;5 &#40;1&#44;3 &#8208; 5&#44;1&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convuls&#245;es &#40;n &#61; 412&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">403 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dismorfias &#40;n &#61; 302&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">293 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dificuldades alimentares &#40;n &#61; 214&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">206 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mamilos invertidos &#40;n &#61; 17&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">8 &#40;16&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">9 &#40;0&#44;6&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">17 &#40;9&#44;5 &#8208; 31&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">11 &#40;4&#44;2 &#8208; 29&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ataxia &#40;n &#61; 107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Hipoglicemia &#40;n &#61; 60&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">7 &#40;14&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">53 &#40;3&#44;5&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;0 &#40;1&#44;9 &#8208; 8&#44;6&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;9 &#40;1&#44;3 &#8208; 6&#44;9&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrofia&#47;Hipoplasia cerebelar &#40;n &#61; 43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;2&#44;5&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9 &#40;1&#44;6 &#8208; 9&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3 &#40;0&#44;06 &#8208; 1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Consanguinidade dos pais &#40;n &#61; 97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcefalia &#40;n &#61; 66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiomiopatia &#40;n &#61; 42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;2&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidropisia fetal n&#227;o imune &#40;n &#61; 22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;1&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Altera&#231;&#245;es esquel&#233;ticas &#40;n &#61; 9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;0&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2417625.png"
              ]
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Resumo dos casos avaliados por isoeletrofocaliza&#231;&#227;o da transferrina em soro no Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Brasil &#40;2008&#8208;2017&#41;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:20 [
            0 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Al Teneiji"
                            1 => "T&#46;U&#46; Bruun"
                            2 => "S&#46; Sidky"
                            3 => "D&#46; Cordeiro"
                            4 => "R&#46;D&#46; Cohn"
                            5 => "R&#46; Mendoza-Londono"
                          ]
                        ]
                      ]
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Artigo Original
Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten‐year experience in a Brazilian center
Isoeletrofocalização da transferrina para investigação das doenças congênitas da glicosilação: análise de dez anos de experiência de um centro brasileiro
Ana Paula Pereira Scholz de Magalhãesa,b, Maira Graeff Burinb, Carolina Fischinger Moura de Souzab, Fernanda Hendges de Bitencourtb, Fernanda Medeiros Sebastiãoa,b, Thiago Oliveira Silvab, Filippo Pinto e Vairod,e, Ida Vanessa Doederlein Schwartza,b,c,
Autor para correspondência
ischwartz@hcpa.edu.br

Autor para correspondência.
a Universidade Federal do Rio Grande do Sul (UFRGS), Programa de Pós‐Graduação em Ciências Médicas, Porto Alegre, RS, Brasil
b Hospital de Clínicas de Porto Alegre (HCPA), Serviço de Genética Médica, Porto Alegre, RS, Brasil
c Universidade Federal do Rio Grande do Sul (UFRGS), Departamento de Genética, Porto Alegre, RS, Brasil
d Mayo Clinic, Departament of Clinical Genomics, Rochester, EUA
e Mayo Clinic, Center for Individualized Medicine, Rochester, EUA
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero de casos que fizeram isoeletrofocaliza&#231;&#227;o da transferrina &#40;IETF&#41; por ano no Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Brasil&#46; Em destaque o n&#250;mero de casos alterados por ano e sua porcentagem&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">As doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o &#40;CDG&#41; s&#227;o doen&#231;as gen&#233;ticas da s&#237;ntese e processamentos dos glicanos das glicoprote&#237;nas e glicolip&#237;dios&#44; de heran&#231;a autoss&#244;mica recessiva em sua maioria&#44; caracterizadas pela defici&#234;ncia total ou parcial de prote&#237;nas envolvidas na glicosila&#231;&#227;o de prote&#237;nas ou lip&#237;dios&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">H&#225; dois tipos principais de glicosila&#231;&#227;o de prote&#237;nas&#58; N&#8208;glicosila&#231;&#227;o e O&#8208; glicosila&#231;&#227;o&#46; A N&#8208;glicosila&#231;&#227;o &#40;liga&#231;&#227;o de N&#8208;glicanos ao grupo amino de asparaginas&#41; compreende uma etapa de montagem e uma etapa de processamento que se estende por tr&#234;s compartimentos&#58; citoplasma&#44; ret&#237;culo endoplasm&#225;tico e complexo de Golgi&#46; A O&#8208;glicosila&#231;&#227;o &#40;liga&#231;&#227;o de O&#8208;glicanos a grupos hidroxila de treoninas ou serinas&#41; n&#227;o apresenta etapa de processamento e consiste apenas na etapa de montagem&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> Dessa forma&#44; existem CDG que envolvem N&#8208;glicosila&#231;&#227;o somente&#44; O&#8208;glicosila&#231;&#227;o somente ou ambas&#46; Estima&#8208;se que 94&#37; dos indiv&#237;duos com CDG apresentem defeitos de N&#8208;glicosila&#231;&#227;o&#44; os mais frequentes s&#227;o a PMM2&#8208;CDG &#40;antiga CDG Ia&#41; e a ALG6&#8208;CDG &#40;antiga CDG Ic&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Desde a primeira descri&#231;&#227;o cl&#237;nica em 1980&#44; mais de 100 tipos de CDG foram identificados &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> As manifesta&#231;&#245;es cl&#237;nicas podem aparecer ainda na gesta&#231;&#227;o&#44; como a hidropisia fetal n&#227;o imune&#44; microcefalia&#44; malforma&#231;&#245;es cong&#234;nitas e dismorfias faciais&#59; em neonatos e na inf&#226;ncia&#44; podem ser encontrados hipoplasia cerebelar&#44; mamilos invertidos&#44; estrabismo&#44; movimentos oculares anormais&#44; retardo de desenvolvimento neuropsicomotor &#40;RDNPM&#41;&#44; hipotonia&#44; ataxia&#44; hiporreflexia&#44; convuls&#245;es&#44; anorexia&#44; v&#244;mitos&#44; diarreia&#44; defeitos do sistema imunol&#243;gico&#44; hipogonadismo&#44; lipodistrofia&#44; hepatomegalia&#44; cifose&#44; escoliose e cardiomiopatia&#46; Podem tamb&#233;m ocorrer fen&#243;tipos mais leves&#44; sem dismorfias e com RNDPM leve&#46; Recomenda&#8208;se&#44; portanto&#44; que a hip&#243;tese de CDG seja considerada em qualquer caso de s&#237;ndrome inexplicada&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao diagn&#243;stico&#44; a isoeletrofocaliza&#231;&#227;o de transferrina &#40;IEFTF&#41; &#233; um teste de triagem para CDGs que envolvem N&#8208;glicosila&#231;&#227;o&#44; pois a transferrina &#233; N&#8208;glicosilada&#46; A IEFTF&#44; nesses casos&#44; mostra um deslocamento cat&#243;dico como consequ&#234;ncia da defici&#234;ncia parcial de &#225;cido si&#225;lico&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A t&#233;cnica detecta dois padr&#245;es de altera&#231;&#227;o&#44; padr&#227;o de altera&#231;&#227;o do tipo 1&#44; associado principalmente a defeitos relacionados ao ret&#237;culo endoplasm&#225;tico &#40;antigamente denominados CDG do tipo I&#41;&#44; e o padr&#227;o do tipo 2&#44; associado&#44; por sua vez&#44; a defeitos relacionados ao sistema Golgi &#40;antigamente denominados CDG do tipo II&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">No Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Rio Grande do Sul &#40;RS&#41;&#44; Brasil &#40;LEIM&#8208;HCPA&#41;&#44; a IEFTF &#233; o &#250;nico exame feito para investiga&#231;&#227;o de CDG&#46; O m&#233;todo usado foi adaptado daquele descrito em 1995 por Hackler&#44; Rolf &#38; Kleine&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Os casos alterados da IEFTF&#44; ou com suspeita de defeitos de O&#8208;glicosila&#231;&#227;o&#44; devem seguir a investiga&#231;&#227;o para fins de confirma&#231;&#227;o diagn&#243;stica&#44; seja por ensaios enzim&#225;ticos&#44; an&#225;lises de espectrometria de massa &#40;ESI&#47;MS&#44; MALDI&#8208;TOF&#41; ou an&#225;lise gen&#233;tica&#46; Frisa&#8208;se que v&#225;rias condi&#231;&#245;es al&#233;m de CDG est&#227;o associadas a resultados alterados na IEFTF&#44; como galactosemia&#44; intoler&#226;ncia heredit&#225;ria &#224; frutose&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;8</span></a> hepatopatias&#44; uso cr&#244;nico e abusivo de &#225;lcool&#44; infec&#231;&#245;es por microrganismos produtores de neuraminidase e polimorfismos da transferrina&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#8211;12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">No Brasil&#44; pouco se sabe sobre a preval&#234;ncia ou incid&#234;ncia de CDG na popula&#231;&#227;o&#44; bem como sobre a disponibilidade dos exames tanto para a triagem como para o diagn&#243;stico dessa doen&#231;a&#46; O objetivo deste estudo foi caracterizar os casos triados pelo exame de IEFTF&#44; de 2008 a 2017&#44; no LEIM&#8208;HCPA&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Metodologia</span><p id="par0045" class="elsevierStylePara elsevierViewall">Estudo observacional e retrospectivo de indiv&#237;duos investigados por IEFTF no LEIM&#8208;HCPA&#44; de 2008 a 2017&#46; Em 2018&#44; foram coletadas e analisadas informa&#231;&#245;es de fichas laboratoriais dos mesmos&#46; O presente estudo foi aprovado pelo comit&#234; de &#233;tica do HCPA com o n&#250;mero 18&#8208;0324&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Coleta de dados</span><p id="par0050" class="elsevierStylePara elsevierViewall">A coleta de dados ocorreu por meio de revis&#227;o das fichas do LEIM&#8208;HCPA&#46; Os seguintes dados foram considerados&#58; data da feitura da IEFTF&#44; idade do indiv&#237;duo no momento&#44; sexo&#44; local de origem&#44; resultado obtido na IEFTF&#44; sinais e sintomas e informa&#231;&#245;es de hist&#243;rico familiar&#46; Al&#233;m disso&#44; para os casos de IEFTF alterados&#44; se houve confirma&#231;&#227;o do diagn&#243;stico de CDG ou de outra doen&#231;a mediante exames complementares&#46; Para os indiv&#237;duos provenientes do HCPA&#44; tamb&#233;m foi feita uma revis&#227;o de prontu&#225;rio eletr&#244;nico dos indiv&#237;duos com resultados alterados&#46; Foram consideradas como n&#227;o existentes as informa&#231;&#245;es pertinentes a este estudo que n&#227;o constavam na ficha laboratorial ou no prontu&#225;rio eletr&#244;nico dos indiv&#237;duos&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise estat&#237;stica</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os bancos de dados foram constru&#237;dos em Microsoft Office Excel 2010 e para a an&#225;lise estat&#237;stica foi usado o programa IBM SPSS Statistics 18&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Os aspectos descritivos foram apresentados nas formas de frequ&#234;ncias para os dados correspondentes &#224; IEFTF nos padr&#245;es normal e alterado&#46; M&#233;dias&#44; desvios&#8208;padr&#227;o&#44; medianas e quartis foram usados para os dados de idade&#46; Para a compara&#231;&#227;o das vari&#225;veis entre os grupos com e sem altera&#231;&#227;o na IEFTF&#44; usou&#8208;se&#44; inicialmente&#44; teste exato de qui&#8208;quadrado de Person&#44; com corre&#231;&#227;o de continuidade&#44; ou exato de Fisher &#40;signific&#226;ncia&#58; p &#60; 0&#44;05&#41;&#46; Posteriormente&#44; foram feitas an&#225;lises residuais &#40;raz&#227;o de preval&#234;ncia bruta e raz&#227;o de preval&#234;ncia ajustada &#8208; regress&#227;o de Poisson com vari&#226;ncia robusta&#41; nos casos com p &#60; 0&#44;05 na an&#225;lise anterior&#46; Foram consideradas como diferindo entre os grupos com IEFTF alterada ou normal somente as vari&#225;veis que apresentaram raz&#227;o de preval&#234;ncia ajustada significativa&#46; Para a an&#225;lise da idade de feitura do teste&#44; foi usado o teste n&#227;o param&#233;trico de Mann&#8208;Whitney&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="par0065" class="elsevierStylePara elsevierViewall">De 2008 a 2017&#44; 1&#46;546 indiv&#237;duos fizeram a IEFTF&#44; 566 &#40;37&#37;&#41; provenientes do RS e 980 &#40;63&#37;&#41; de outros estados do Brasil &#91;Santa Catarina&#47;Paran&#225;&#58; 62 &#40;4&#37;&#41;&#59; Regi&#227;o Sudeste 744 &#40;48&#37;&#41;&#59; Nordeste 77 &#40;5&#37;&#41;&#59; Centro&#8208;Oeste 64 &#40;4&#37;&#41;&#59; Norte 33 &#40;2&#37;&#41;&#93;&#46; A m&#233;dia anual do n&#250;mero de casos investigados foi de 156 &#177; 49&#47;casos por ano e&#44; desses&#44; 5 &#177; 2&#44;8 casos&#47;ano com IEFTF alterada&#46; O maior n&#250;mero de casos investigados foi em 2012 &#40;246&#41; e em 2017 o maior n&#250;mero de casos alterados &#40;11&#41;&#46; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Dos indiv&#237;duos&#44; 51 &#40;3&#37;&#59; RS &#61; 23&#41; apresentaram altera&#231;&#227;o no exame IEFTF&#46; Desses&#44; 14 &#40;28&#37;&#41; tiveram a investiga&#231;&#227;o conclu&#237;da &#40;RS &#61; 11&#41;&#44; quatro &#40;RS &#61; 3&#41; chegaram ao diagn&#243;stico confirmat&#243;rio de CDG por an&#225;lise gen&#233;tica &#40;MPDU1&#8208;CDG &#61; 1&#44; SLC35A2&#8208;CDG &#61; 1&#44; PMM2&#8208;CDG &#61; 2&#41;&#46; Para os casos restantes&#44; exames complementares permitiram a exclus&#227;o de CDG e o diagn&#243;stico confirmat&#243;rio de outras doen&#231;as&#58; galactosemia cl&#225;ssica &#40;n &#61; 4&#44; todos confirmados por meio da medida da atividade da Gal1PUT&#41;&#44; intoler&#226;ncia heredit&#225;ria &#224; frutose &#40;n &#61; 4&#44; todos confirmados por an&#225;lise gen&#233;tica&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41; e dois casos de doen&#231;a peroxissomal &#40;ambos confirmados por medida de &#225;cidos graxos de cadeia muito longa&#41;&#46; Para os 37 casos restantes&#44; n&#227;o foi poss&#237;vel a obten&#231;&#227;o de informa&#231;&#245;es adicionais acerca da conclus&#227;o diagn&#243;stica&#46; Considerando apenas os casos do RS&#44; dos 566 casos investigados por IEFTF&#44; 23 apresentaram padr&#227;o alterado &#40;4&#37;&#41; e 11&#47;23 &#40;48&#37;&#41; tiveram o diagn&#243;stico de alguma doen&#231;a confirmado &#40;CDG &#61; 3&#47;11 ou 27&#37;&#41;&#46; A <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a> apresenta o perfil completo dos indiv&#237;duos inclu&#237;dos no estudo&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">A faixa de 11 a 36 meses foi a que apresentou a maior preval&#234;ncia de resultados alterados&#44; 48&#37; dos indiv&#237;duos que apresentaram resultado alterado encontram&#8208;se nessa faixa et&#225;ria&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A manifesta&#231;&#227;o cl&#237;nica mais comum nos casos investigados foi RDNPM&#44; seguido de convuls&#245;es&#44; hipotonia&#44; defici&#234;ncia intelectual e dismorfias&#46; Por&#233;m&#44; os sintomas mais frequentes nos casos com altera&#231;&#245;es na IEFTF foram&#58; RDNPM&#44; hipotonia&#44; hepatopatia&#44; defici&#234;ncia intelectual e hepatomegalia&#44; foram mamilos invertidos &#40;raz&#227;o de preval&#234;ncia ajustada &#61; 11&#41;&#44; seguidos de hepatopatia&#44; hipoglicemia&#44; altera&#231;&#245;es oftalmol&#243;gicas e recorr&#234;ncia familial &#224;s manifesta&#231;&#245;es cl&#237;nicas estatisticamente associadas &#224; IEFTF alterada &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discuss&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">CDGs t&#234;m sido descritas como um grande desafio diagn&#243;stico&#44; uma vez que&#44; nesse conjunto de doen&#231;as&#44; quase todos os &#243;rg&#227;os s&#227;o acometidos e uma grande variedade de sintomas j&#225; foi descrita&#46; Assim&#44; a recomenda&#231;&#227;o &#233; considerar CDG em qualquer caso de doen&#231;a n&#227;o explicada&#44; principalmente quando h&#225; presen&#231;a de sintomas neurol&#243;gicos&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> No Brasil&#44; um outro fator que contribui para a dificuldade diagn&#243;stica &#233; a dificuldade de acesso a exames confirmat&#243;rios&#46; Dentro desse contexto&#44; nossos dados sugerem que existe subdiagn&#243;stico de CDG no Brasil e que esfor&#231;os devem ser feitos para a implanta&#231;&#227;o dos testes diagn&#243;sticos&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O protocolo de investiga&#231;&#227;o para CDG estabelecido no HCPA n&#227;o contempla uma investiga&#231;&#227;o completa para a doen&#231;a&#44; uma vez que somente a IEFTF &#233; oferecida&#46; O protocolo mais custo&#8208;efetivo&#44; ap&#243;s terem sido descartadas outras doen&#231;as que possam causar altera&#231;&#227;o da IEFTF&#44; n&#227;o est&#225; bem estabelecido&#46; Uma estrat&#233;gia poss&#237;vel seria o sequenciamento inicial apenas do gene <span class="elsevierStyleItalic">PMM2</span> para os casos alterados com padr&#227;o de CDG tipo I&#44; uma vez que esses s&#227;o os casos mais frequentes de CDG&#46; Se o sequenciamento n&#227;o evidenciar anormalidade&#44; uma an&#225;lise de painel com genes espec&#237;ficos para CDG e&#44; em caso de resultado negativo&#44; o sequenciamento completo do exoma estariam indicados&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> Outra estrat&#233;gia poss&#237;vel seria a investiga&#231;&#227;o inicial direta por meio de painel inclu&#237;dos os genes causadores de CDG&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Apesar de as CDG serem doen&#231;as gen&#233;ticas raras&#44; existe um n&#250;mero significativo de indiv&#237;duos com suspeita da doen&#231;a&#44; como pode ser visto pela m&#233;dia anual de casos investigados por IEFTF no LEIM&#8208;HCPA&#46; Entretanto&#44; o n&#250;mero de casos confirmados foi pequeno &#40;apenas 4 indiv&#237;duos em dez anos&#41;&#44; o que sugere a ocorr&#234;ncia de um subdiagn&#243;stico dessas doen&#231;as em nosso pa&#237;s&#44; ainda mais considerando que a frequ&#234;ncia estimada para PMM2&#8208;CDG&#44; que vem ser a CDG mais comum&#44; &#233; de cerca de 1&#47;20&#46;000 rec&#233;m&#8208;nascidos&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> Mesmo na aus&#234;ncia de tratamento espec&#237;fico para a maioria das CDG&#44; a confirma&#231;&#227;o do seu diagn&#243;stico &#233; fundamental para o aconselhamento gen&#233;tico&#44; haja vista o elevado risco de recorr&#234;ncia &#40;a maioria das CDG apresenta padr&#227;o de heran&#231;a autoss&#244;mico recessivo ou ligado ao X&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Nosso estudo mostrou&#44; tamb&#233;m&#44; que galactosemia cl&#225;ssica e intoler&#226;ncia heredit&#225;ria &#224; frutose s&#227;o causas frequentes de altera&#231;&#245;es na IEFTF&#46; Galactosemia tem sido referida como um segundo tipo de defeito de glicosila&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;7</span></a> A literatura aponta que h&#225; anormalidades na glicosila&#231;&#227;o de N&#8208;glicanos na transferrina s&#233;rica em neonatos com galactosemia n&#227;o tratados&#46; Essas anormalidades&#44; em sua grande parte&#44; s&#227;o resolvidas com o tratamento diet&#233;tico com restri&#231;&#227;o de galactose&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">7&#44;15&#44;16</span></a> Outra doen&#231;a que pode acarretar em hipoglicosila&#231;&#227;o das isoformas de transferrina &#233; a intoler&#226;ncia heredit&#225;ria &#224; frutose&#46; &#201; causada por uma defici&#234;ncia na atividade da enzima aldolase B&#59; consequentemente&#44; a frutose&#8208;1P &#233; acumulada em c&#233;lulas hep&#225;ticas&#44; acarreta a inibi&#231;&#227;o da atividade da fosfomanose isomerase&#44; enzima presente nas primeiras etapas da glicosila&#231;&#227;o de prote&#237;nas&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Por outro lado&#44; tendo&#8208;se em considera&#231;&#227;o que o f&#237;gado &#233; um dos principais &#243;rg&#227;os de glicosila&#231;&#227;o&#44; tamb&#233;m respons&#225;vel pela produ&#231;&#227;o da maioria das prote&#237;nas s&#233;ricas glicosiladas&#44; defeitos de glicosila&#231;&#227;o est&#227;o associados a sintomas cl&#237;nicos hep&#225;ticos&#44; os quais est&#227;o presentes em torno de 20&#37; dos casos de CDG&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Nosso estudo corrobora esses achados&#44; visto que as hepatopatias apresentam forte associa&#231;&#227;o com altera&#231;&#245;es no padr&#227;o da IEFTF &#40;indiv&#237;duos com hepatopatia t&#234;m 4&#44;6 vezes mais chances de apresentar uma altera&#231;&#227;o na IEFTF do que indiv&#237;duos sem esse sintoma&#41;&#46; Hepatopatias est&#227;o associadas a resultados alterados na IEFTF&#44; por&#233;m essa altera&#231;&#227;o pode n&#227;o estar diretamente associada &#224;s CDG&#44; e sim a outros EIM que afetam o f&#237;gado&#44; como as doen&#231;as peroxissomais&#44; identificadas em dois casos com altera&#231;&#227;o da IEFTF no nosso estudo&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">O fato de que faixa de 11 a 36 meses foi a que apresentou a maior preval&#234;ncia de resultados alterados da IEFTF sugere que as condi&#231;&#245;es causadoras de altera&#231;&#245;es na IEFTF &#40;entre elas&#44; as CDG&#41; apresentam&#8208;se principalmente na inf&#226;ncia&#44; ap&#243;s o per&#237;odo de lact&#226;ncia&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nossos dados mostram que a presen&#231;a de mamilos invertidos apresentou o maior &#237;ndice de associa&#231;&#227;o com a altera&#231;&#227;o da IEFTF &#40;a raz&#227;o de preval&#234;ncia ajustada demonstra que esse sintoma aumenta em 11 vezes a chance de o indiv&#237;duo apresentar a IEFTF alterada&#41;&#46; Mamilos invertidos est&#227;o geralmente presentes em indiv&#237;duos com CDG ao nascimento&#44; podem voltar &#224; posi&#231;&#227;o normal em poucos dias ou semanas de vida&#46; Entretanto&#44; a persist&#234;ncia do achado na vida adulta pode ocorrer&#46; &#201; importante salientar&#44; no entanto&#44; que a lista de s&#237;ndromes associadas a mamilos invertidos &#233; extensa&#44; inclui&#44; por exemplo&#44; s&#237;ndromes de Turner&#44; de Smith&#8208;Lemli&#8208;Optiz e de Robinow&#44; entre outras&#44; por&#233;m&#44; tamb&#233;m pode ser observado em indiv&#237;duos normais&#46; No caso das CDG&#44; os mamilos invertidos s&#227;o encontrados com maior frequ&#234;ncia em indiv&#237;duos com defeitos de N&#8208;glicosila&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o &#224;s limita&#231;&#245;es do estudo&#44; &#233; importante mencionar que est&#225; baseado em informa&#231;&#245;es cl&#237;nicas presentes nos prontu&#225;rios dos indiv&#237;duos com suspeita de CDG&#46; Outra limita&#231;&#227;o importante&#44; com rela&#231;&#227;o aos indiv&#237;duos provenientes de outras regi&#245;es do pa&#237;s&#44; &#233; que&#44; ap&#243;s a libera&#231;&#227;o do laudo aos servi&#231;os de origem do paciente&#44; n&#227;o temos informa&#231;&#245;es do seguimento que esses indiv&#237;duos tiveram&#44; ou seja&#44; se o paciente concluiu a investiga&#231;&#227;o ou n&#227;o&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclus&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">Apesar das limita&#231;&#245;es do estudo no que diz respeito &#224; an&#225;lise retrospectiva dos casos&#44; mediante revis&#227;o de prontu&#225;rios e a falta de uniformiza&#231;&#227;o do atendimento e diagn&#243;stico dos pacientes provenientes de diferentes regi&#245;es do pa&#237;s&#44; verificou&#8208;se que h&#225; necessidade da implanta&#231;&#227;o de novas t&#233;cnicas para diagn&#243;stico de CDG e o estabelecimento de um protocolo mais completo para a investiga&#231;&#227;o das CDG no LEIM&#8208;HCPA&#46; Os achados mostram que&#44; apesar de altera&#231;&#245;es na IEFTF terem sido reportadas em 51 casos&#44; conseguimos constatar em apenas quatro indiv&#237;duos o diagn&#243;stico confirmado para CDG&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Os dados obtidos tamb&#233;m mostram que os principais sintomas que levaram &#224; suspeita de CDG foram neurol&#243;gicos&#46; No entanto&#44; os indiv&#237;duos que apresentarem mamilos invertidos&#44; hepatopatia&#44; hipoglicemia&#44; altera&#231;&#245;es oftalmol&#243;gicas e a presen&#231;a de outros casos na fam&#237;lia foram os que tiveram maior probabilidade de ter IEFTF alterada&#46; Dessa forma&#44; a triagem para CDG deve ser especialmente considerada quando houver a presen&#231;a dessas manifesta&#231;&#245;es cl&#237;nicas&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Financiamento</span><p id="par0130" class="elsevierStylePara elsevierViewall">Fundo de Incentivo &#224; Pesquisa e Eventos do Hospital de Cl&#237;nicas de Porto Alegre &#40;FIPE&#8208;HCPA&#41;&#44; n&#250;mero do financiamento&#58; 18&#8208;0324&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflitos de interesse</span><p id="par0135" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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    "fechaRecibido" => "2019-02-18"
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            0 => "Isoelectric focusing"
            1 => "Transferrin"
            2 => "Congenital disorders of glycosylation"
            3 => "Screening"
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            0 => "Isoeletrofocaliza&#231;&#227;o"
            1 => "Transferrina"
            2 => "Doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To characterize cases of suspected congenital disorders of glycosylation &#40;CDG&#41; investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Observational&#44; cross&#8208;sectional&#44; retrospective study&#46; The laboratory records of 1&#44;546 individuals &#40;median age &#61; 36 months&#44; 25&#8208;75 IQR &#61; 10&#8208;108&#59; males &#61; 810&#41; submitted to the TfIEF test during the period were reviewed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Fifty&#8208;one individuals &#40;3&#37;&#41; had an altered TfIEF pattern &#40;5 &#177; 2&#46;8 cases&#47;year&#59; median age &#61; 24 months&#44; 25&#8208;75 IQR &#61; 11&#8208;57 months&#59; males &#61; 27&#44; 53&#37;&#41;&#46; For 14 of them&#44; data on diagnosis conclusion were available &#40;classic galactosemia &#61; 4&#59; hereditary fructose intolerance &#61; 4&#59; peroxisomal diseases &#61; 2&#59; PMM2&#8208;CDG &#61; 2&#59; MPDU1&#8208;CDG &#61; 1&#59; SLC35A2&#8208;CDG &#61; 1&#41;&#46;Comparing the cases with the normal and altered TfIEF patterns&#44; there was a higher prevalence of altered cases in the age group from 11 months to 3 years&#46; There was an increase in the likelihood of change in TfIEF&#44; especially in the presence of inverted nipples or liver disease&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The data suggest that the investigation of a case with suspected CDG is a complex problem&#44; being aggravated by the existence of other IEMs &#40;inborn errors of metabolism&#41; associated with altered TfIEF pattern and lack of access to confirmatory tests&#46; The presence of inverted nipples and liver disease&#44; especially in individuals aged 11 months to 3 years&#44; should suggest the need for TfIEF investigation&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Caracterizar os casos com suspeita de CDG investigados em laborat&#243;rio do sul do Brasil pelo exame de IEFTF de 2008 a 2017&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodologia</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional&#44; transversal&#44; retrospectivo&#46; Foram revisadas as fichas laboratoriais de 1&#46;546 indiv&#237;duos &#40;mediana de idade &#61; 36 meses&#44; IQ 25&#8208;75 &#61; 10&#8208;108&#59; sexo masculino &#61; 810&#41; que fizeram o exame de IEFTF no per&#237;odo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cinquenta e um indiv&#237;duos &#40;3&#37;&#41; apresentaram padr&#227;o alterado na IEFTF &#40;5 &#177; 2&#44;8 casos&#47;ano&#59; mediana de idade &#61; 24 meses&#44; IQ 25&#8208;75 &#61; 11&#8208;57 meses&#59; sexo masculino &#61; 27&#44; 53&#37;&#41;&#46; Para 14 deles&#44; estavam dispon&#237;veis dados sobre a conclus&#227;o do diagn&#243;stico &#40;galactosemia cl&#225;ssica &#61; 4&#59; intoler&#226;ncia heredit&#225;ria &#224; frutose &#61; 4&#59; doen&#231;as peroxissomais &#61; 2&#59; PMM2&#8208;CDG &#61; 2&#59; MPDU1&#8208;CDG &#61; 1&#59; SLC35A2&#8208;CDG &#61; 1&#41;&#46; Comparando os casos com padr&#227;o normal e alterado na IEFTF&#44; houve maior preval&#234;ncia de casos alterados na faixa et&#225;ria de 11 meses a 3 anos&#46; Verificou&#8208;se um aumento na probabilidade de altera&#231;&#227;o na IEFTF principalmente na presen&#231;a de mamilos invertidos ou de hepatopatia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os nossos dados sugerem que a investiga&#231;&#227;o de um caso com suspeita de CDG &#233; complexa&#44; &#233; agravada pela exist&#234;ncia de outros EIM associados a padr&#227;o alterado na IEFTF e pela falta de acesso a exames confirmat&#243;rios&#46; A presen&#231;a principalmente de mamilos invertidos e de hepatopatia em indiv&#237;duos na faixa et&#225;ria de 11 meses a 3 anos deve sugerir a necessidade de investiga&#231;&#227;o por IEFTF&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Estudo feito na Universidade Federal do Rio Grande do Sul &#40;UFRGS&#41;&#44; Hospital de Cl&#237;nicas de Porto Alegre &#40;HCPA&#41;&#44; Porto Alegre&#44; RS&#44; Brasil&#46;</p>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero de casos que fizeram isoeletrofocaliza&#231;&#227;o da transferrina &#40;IETF&#41; por ano no Laborat&#243;rio de Erros Inatos do Metabolismo do Hospital de Cl&#237;nicas de Porto Alegre&#44; Brasil&#46; Em destaque o n&#250;mero de casos alterados por ano e sua porcentagem&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ERGIC&#44; compartimento intermedi&#225;rio do ret&#237;culo endoplasm&#225;tico&#8208;Golgi&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Os tipos de CDG em negrito correspondem a casos diagnosticados na presente coorte&#46; A nomenclatura das CDG segue com o nome do gene onde ocorre a muta&#231;&#227;o hifenizado com CDG&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Fonte dos dados&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#8211;12</span></a></p>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GMPPA&#8208;CDGGMPPB&#8208;CDGMPI&#8208;CDG<span class="elsevierStyleBold">PMM2&#8208;CDG</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EOGT&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DHDDS&#8208;CDG NANS&#8208;CDGCAD&#8208;CDG PGM1&#8208;CDGGFPT1&#8208;CDG PGM3&#8208;CDGGNE&#8208;CDG CPS2&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ret&#237;culo endoplasm&#225;tico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALG1&#8208;CDG DPAGT1&#8208;CDGALG2&#8208;CDG MOGS&#8208;CDGALG3&#8208;CDG GANAB&#8208;CDGALG6&#8208;CDG PRKCSH&#8208;CDGALG8&#8208;CDG PRKCSH&#8208;CDGALG9&#8208;CDG RFT1&#8208;CDGALG11&#8208;CDG STT3A&#8208;CDGALG12&#8208;CDG STT3B&#8208;CDGALG13&#8208;CDG SSR3&#8208;CDGALG14&#8208;CDG SSR4&#8208;CDGDDOST&#8208;CDG TUSC3&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC35D1&#8208;CDGPOGLUT1&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PIGA&#8208;CDGPIGC&#8208;CDGPIGG&#8208;CDGPIGL&#8208;CDGPIGM&#8208;CDGPIGN&#8208;CDGPIGO&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PIGQ&#8208;CDGPIGT&#8208;CDGPIGV&#8208;CDGPIGW&#8208;CDGPIGY&#8208;CDGPGAP1&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DOLK&#8208;CDGNUS1&#8208;CDGSRD5A3&#8208;CDGDPM1&#8208;CDGDPM2&#8208;CDGDPM3&#8208;CDG<span class="elsevierStyleBold">MPDU1&#8208;CDG</span>ATP6AP1&#8208;CDGTRAPPC11&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Golgi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MAN1B1&#8208;CDGMGAT2&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALT7&#8208;CDG XYLT1&#8208;CDGB3GALT6&#8208;CDG XYLT2&#8208;CDGB3GAT3&#8208;CDG GALNT3&#8208;CDGCHSY1&#8208;CDG LFNG&#8208;CDGEXT1&#8208;CDG POFUT1&#8208;CDGEXT2&#8208;CDGB3GALTL&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALNT1&#8208;CDGST3GAL5&#8208;CDGPGAP2&#8208;CDGPGAP3&#8208;CDG</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B4GALT1&#8208;CDG COG4&#8208;CDGST3GAL3&#8208;CDG COG5&#8208;CDGSLC35A1&#8208;CDG COG6&#8208;CDG<span class="elsevierStyleBold">SLC35A2&#8208;CDG</span> COG7&#8208;CDGSLC35A3&#8208;CDG COG8&#8208;CDGSLC35C1&#8208;CDG ATP6V0A2&#8208;CDGCOG1&#8208;CDG TIMEM165&#8208;CDGCOG2&#8208;CD VPS138&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ERGIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SEC23B&#8208;CDGCCDC115&#8208;CDGTMEM199&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Membrana plasm&#225;tica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC39A8&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Membrana do sarcolema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#95;&#95;&#95;&#95;&#95;&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B3GALNT2&#8208;CDGFKTN&#8208;CDGFKRP&#8208;CDGISPD&#8208;CDGLARGE&#8208;CDGPOMGNT1&#8208;CDGPOMT1&#8208;CDGPOMT2&#8208;CDGTMEM5&#8208;CDGPOMK&#8208;CDG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2417624.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Exemplos de doen&#231;as cong&#234;nitas da glicosila&#231;&#227;o &#40;CDG&#41; descritas de acordo com sua localiza&#231;&#227;o celular e as diferentes vias de glicosila&#231;&#227;o</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AR&#44; autoss&#244;mica recessiva&#59; F&#44; feminino&#59; LX&#44; ligada ao X&#59; M&#44; masculino&#59; MG&#44; Minas Gerais&#59; Pac&#44; paciente&#59; RDNPM&#44; retardo do desenvolvimento neuropsicomotor&#59; RS&#44; Rio Grande do Sul&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pac&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Idade ao diagn&#243;stico &#40;meses&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Origem&#40;Estado&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Consanguinidadeparental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Manifesta&#231;&#245;escl&#237;nicas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CDG &#40;heran&#231;a&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gen&#243;tipo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiomiopatia&#44; mamilos invertidos&#44; RDNPM&#44; dificuldades alimentares&#44; hipotonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PMM2&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;193G&#62;T&#47;422G&#62;A &#47; p&#46;Asp65Tyr&#47;Arg141His&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mamilos invertidos&#44; altera&#231;&#245;es esquel&#233;ticas&#44; RDNPM&#44; defici&#234;ncia intelectual&#44; altera&#231;&#245;es oftalmol&#243;gicas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PMM2&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;193G&#62;T&#47;422G&#62;A &#47; p&#46;Asp65Tyr&#47;Arg141His&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o dispon&#237;veis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MPDU1&#8208;CDG &#40;AR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o dispon&#237;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dismorfias&#44; RDNPM&#44; convuls&#245;es&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SLC35A2 &#8211; CDG &#40;LX&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;128T&#62;C &#40;p&#46;Leu43Pro&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">IC&#44; intervalo de confian&#231;a&#59; IETFTF&#44; isoeletrofocaliza&#231;&#227;o da transferrina&#59; M&#44; sexo masculino&#59; NC&#44; n&#227;o calculado&#59; RDNPM&#44; retardo do desenvolvimento neuropsicomotor&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Compara&#231;&#227;o feita entre os casos com padr&#227;o normal e padr&#227;o alterado na IEFTF&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span> 10 casos que n&#227;o tiveram o sexo do indiv&#237;duo informado&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Para as compara&#231;&#245;es&#44; inicialmente foi usado o teste do qui&#8208;quadrado de Person com corre&#231;&#227;o de continuidade&#44; ou o teste exato de Fisher &#40;<span class="elsevierStyleSup">c</span> resultados significativos&#44; p &#60; 0&#44;05&#41;&#59; ap&#243;s&#44; foi calculada a raz&#227;o de preval&#234;ncia bruta para as vari&#225;veis com p &#60; 0&#44;05 e&#44; para as vari&#225;veis com diferen&#231;as significativas na raz&#227;o de preval&#234;ncia bruta&#44; foi calculada a raz&#227;o de preval&#234;ncia ajustada&#46; As vari&#225;veis em negrito s&#227;o aquelas que apresentaram raz&#227;o de preval&#234;ncia ajusta estatisticamente significativa&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Manifesta&#231;&#245;es cl&#237;nicas&#40;n &#61; 1&#46;546indiv&#237;duos&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IEFTFPadr&#227;o alterado&#40;n &#61; 51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IEFTFPadr&#227;o normal&#40;n &#61; 1&#46;495&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Raz&#227;o de preval&#234;ncia bruta&#40;IC&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Raz&#227;o de preval&#234;ncia ajustada&#40;IC&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediana de idade &#40;meses&#41; &#40;IQ 25 &#8211; 75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;11 &#8208; 57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;10 &#8208; 108&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sexo masculino &#40;n &#61; 810&#47; 1536<span class="elsevierStyleSup">b</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;54&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">783 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RDNPM &#40;n &#61; 625&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">598 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hipotonia &#40;n &#61; 326&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">307 &#40;20&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;3 &#40;1&#44;3 &#8208; 4&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5 &#40;0&#44;8 &#8208; 2&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Hepatopatias &#40;n &#61; 131&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">18 &#40;35&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">113 &#40;7&#44;5&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">6&#44;1 &#40;3&#44;5 &#8208; 10&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;6 &#40;2&#44;5 &#8208; 8&#44;7&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Defici&#234;ncia intelectual &#40;n &#61; 317&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">302 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatomegalia &#40;n &#61; 153&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139 &#40;9&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;5 &#40;1&#44;9 &#8208; 6&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;1 &#40;0&#44;5 &#8208; 2&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Altera&#231;&#245;es oftalmol&#243;gicas &#40;n &#61; 93&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">12 &#40;24&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">81 &#40;5&#44;4&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;9 &#40;2&#44;7 &#8208; 9&#44;1&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;8 &#40;1&#44;3 &#8208; 6&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Recorr&#234;ncia familial &#40;n &#61; 115&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">11 &#40;22&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">104 &#40;6&#44;9&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">3&#44;5 &#40;1&#44;8 &#8208; 6&#44;7&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;5 &#40;1&#44;3 &#8208; 5&#44;1&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Convuls&#245;es &#40;n &#61; 412&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">403 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dismorfias &#40;n &#61; 302&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">293 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dificuldades alimentares &#40;n &#61; 214&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">206 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mamilos invertidos &#40;n &#61; 17&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">8 &#40;16&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">9 &#40;0&#44;6&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">17 &#40;9&#44;5 &#8208; 31&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">11 &#40;4&#44;2 &#8208; 29&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ataxia &#40;n &#61; 107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Hipoglicemia &#40;n &#61; 60&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">7 &#40;14&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">53 &#40;3&#44;5&#37;&#41;</span><span class="elsevierStyleSup"><span class="elsevierStyleBold">c</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;0 &#40;1&#44;9 &#8208; 8&#44;6&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#44;9 &#40;1&#44;3 &#8208; 6&#44;9&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrofia&#47;Hipoplasia cerebelar &#40;n &#61; 43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;2&#44;5&#37;&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;9 &#40;1&#44;6 &#8208; 9&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3 &#40;0&#44;06 &#8208; 1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Consanguinidade dos pais &#40;n &#61; 97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcefalia &#40;n &#61; 66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiomiopatia &#40;n &#61; 42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;2&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidropisia fetal n&#227;o imune &#40;n &#61; 22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;1&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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ISSN: 22555536
Idioma original: Português
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