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Nutrition in phenylketonuria

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Abstract

The same basic principles are used to deliver dietary treatment in PKU that was developed sixty years ago. Dietary treatment is undoubtedly very successful, but it has gradually evolved and been guided commonly by individual experience and expert opinion only. There is little international consensus about dietary practice with improvements in specialist dietary products concentrating on taste and presentation rather than nutritional composition. Many areas of dietary treatment have not been rigorously examined. In particular, the amino acid and micronutrient profile of Phenylalanine-free (phe-free) amino acids requires further study. In different formulations of phe-free amino acids, there are variations in the amino acid patterns as well the amount of essential and non essential amino acids per 100 g/amino acids. The amount of added tyrosine and branch chain amino varies substantially, and in PKU specifically, there is little data about their relative absorption rates and bioavailability. In phe-free amino acids, there is evidence suggesting that some of the added micronutrients may be excessive and so the source and amount of each micronutrient should be scrutinized, with a need for the development of international nutritional composition standards exclusively for these products. There is a dearth of data about the life-long phenylalanine tolerance of patients or the nutritional state of adult patients treated with diet. There is a growing need to measure body composition routinely in children with PKU and with the rise in childhood obesity, it is important to measure body fatness and identify those who are at greatest risk of ‘co-morbidities’ of obesity. There is necessity for international collaboration to ensure robust data is collected on many basic aspects of nutritional care to guarantee that diet therapy is delivered to the highest standard.

Highlights

► Consensus on dietary management of PKU is limited. ► Life long information about changes in phenylalanine tolerance is lacking in PKU. ► The amino acid and micronutrient composition of phe-free amino acids requires further examination. ► There is inadequate evidence to define optimal tyrosine supplementation in PKU. ► It is unknown if the low phenylalanine diet prescribed in infancy may increase the risk of other metabolic disturbances in later life.

Introduction

Phenylketonuria (PKU) is a genetic disorder first treated with a low phenylalanine diet sixty years ago, and more recently with the drug BH4. Diet therapy and nutrition remain a central focus in the treatment of PKU and diet has seen many improvements both in terms of nutritional quality and palatability of specialist dietary products. However, there are many areas where either limited knowledge about the nutritional needs of the normal ‘healthy’ population and unreliable or under-developed tools to assess nutritional status have hampered progress in developing diet therapy further. In addition, some areas of diet therapy have not received rigorous examination and much existing practice is based on years of experience rather than robust evidence. In this review, we will assess present knowledge concerning protein, amino acids, vitamin and trace element status, in addition to examining the growth and body composition of patients with PKU.

Section snippets

Protein requirements

The primary function of dietary protein is to provide amino acids for growth, renewing tissue protein and synthesizing specific nitrogen-containing products [1]. After ingestion, proteins are denatured in the stomach and pass into the small intestine, where the resultant mixture of free amino acids and small peptides is then transported into the enteral cells and secreted as free amino acids into the bloodstream or further metabolized within the gut or liver itself [2]. Protein intake as free

Dietary phenylalanine

In patients with severe PKU, there is a negligible or very minimal capacity to oxidize phenylalanine. Phenylalanine is an indispensable, aromatic amino acid. It is essential for protein synthesis and to maintain phenylalanine homeostasis [27] with the remainder being hydroxylated to tyrosine. In non PKU, in vivo studies indicate that 27–41% of l-phenylalanine is converted into tyrosine within 5–8 h of intake [28], [29].

Longitudinal growth

In the early years of treating PKU, the desire to achieve normal phenylalanine concentrations, using very restrictive diet therapy, led to growth impairment [50] and malnutrition, probably with a secondary negative effect on intellectual function [44]. In the 1990's, poor linear and head circumference growth were reported in German children with mean protein intakes ranging from 2.24 g/kg/body weight until 2 years of age and about 1.98 g/kg/body weight until 6 years (energy intakes were not

Micronutrient status in PKU

In a low phenylalanine diet, animal proteins act as the vectors for many micronutrients, and to avoid their deficiency, vitamins, minerals and trace minerals must be supplemented in the diet (mainly through the phe-free amino acids). In PKU, the micronutrient status is influenced by many factors: type of diet, amount of natural protein [animal or vegetable origin], BH4 treatment, metabolic control, micronutrient composition of the phe-free amino acids, and frequency of their dosage. Patients

Recommendations

  • Alternative ‘intact’ protein substitute sources should be explored and developed, as they are likely to be associated with improved protein utilization and dietary adherence.

  • Further controlled studies are required examining the ideal dosage of phe-free amino acids particularly the relationship between dosage and improved tolerance of dietary phenylalanine.

  • The amino acid profile and micronutrient composition of the phe-free amino acids should be re-examined to develop products that better meet

Conclusions

Nutrition and dietary management in PKU must continue to develop with heightened momentum and in conjunction with the new non-diet treatments. It is important to collect robust evidence about the protein, amino acid, micronutrient requirements together with full knowledge about the growth and body composition of patients with PKU. This will provide essential data to act as a benchmark to compare the outcome of alternative treatments. International standards should be introduced to regulate the

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