Recommendations for the nutrition management of phenylalanine hydroxylase deficiency

Abstract

The effectiveness of a phenylalanine-restricted diet to improve the outcome of individuals with phenylalanine hydroxylase deficiency (OMIM no. 261600) has been recognized since the first patients were treated 60 years ago. However, the treatment regime is complex, costly, and often difficult to maintain for the long term. Improvements and refinements in the diet for phenylalanine hydroxylase deficiency have been made over the years, and adjunctive therapies have proven to be successful for certain patients. Yet evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking. Thus, recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys. The areas investigated included choice of appropriate medical foods, integration of adjunctive therapies, treatment during pregnancy, monitoring of nutritional and clinical markers, prevention of nutrient deficiencies, providing of access to care, and compliance strategies. This process has not only provided assessment and refinement of current nutrition management and monitoring recommendations but also charted a direction for future studies. This document serves as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylalanine hydroxylase deficiency.Genet Med 16 2, 121–131.

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

“…Detailed dietary management of PAH deficiency is described in the accompanying nutrition recommendations authored by the Genetic Metabolic Dietitians International and Southeast Regional Newborn Screening and Genetics Collaborative. 29 The dietary reference intakes for the general population are modified for individuals with PAH deficiency by adding specific recommendations for PHE, TYR, and protein ( Table 1; see companion paper from the Genetic Metabolic Dietitians International/Southeast Regional Newborn Screening and Genetics Collaborative for references). The wide ranges given for PHE intake reflect the influence of many factors on PHE requirements, including residual PAH deficiency activity, patient age, growth rate, sapropterin-responsiveness, etc.…”

“…56 Please see the accompanying Genetic Metabolic Dietitians International document for details on available supplements and recommended monitoring. 29 Postpartum maternal PHE requirements will decrease from the increased anabolic requirements of the third trimester, and careful metabolic and nutritional monitoring should continue. Use of medical food may provide the increased calories and protein required to support breastfeeding (640 kcal/day and 25 g protein/day).…”

Parenteral Nutrition in the Newborn: Associated Disorders and Nutritional Aspects

“…With the advent of new technologies in the production of concentrated/isolated food compounds for nutritional therapy, investigators seek to highlight the participation of specific lipids in the recovery of several bouts. Recent evidence indicates that long-chain polyunsaturated fatty acids play an important role in the treatment of IEM [52] and morphological development of the CNS [53].…”

Neuropsychological assessment among children and adolescents with phenylketonuria and hyperphenylalaninemia and its relationship with plasma phenylalanine levels

“…According to the American recommendation, the value should be maintained between 2 mg/dL and 6 mg/dL. 3 However, in Europe, the recommendation is to keep values < 4 mg/dL. 4 There is agreement, h o w e v e r , i n t h e i m p o r t a n c e o f keeping these levels not only during childhood, but along the patient's life.…”

“…3 A prescribed diet is recommended for patients with phenylalanine levels < 6 mg/dL, as well as frequent monitoring for those who have in their first years of life values between 2 mg/dL and 6 mg/dL, to determine whether it is necessary to start a diet due to disease related decompensations that are typical of this age. 1 Recommendations related to limits for phenylalanine levels are being reviewed.…”