Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. If left untreated, PKU results in increased phenylalanine concentrations in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. PKU management differs widely across Europe and therefore these guidelines have been developed aiming to optimize and standardize PKU care. Professionals from 10 different European countries developed the guidelines according to the AGREE (Appraisal of Guidelines for Research and Evaluation) method. Literature search, critical appraisal and evidence grading were conducted according to the SIGN (Scottish Intercollegiate Guidelines Network) method. The Delphi-method was used when there was no or little evidence available. External consultants reviewed the guidelines. Using these methods 70 statements were formulated based on the highest quality evidence available. The level of evidence of most recommendations is C or D. Although study designs and patient numbers are sub-optimal, many statements are convincing, important and relevant. In addition, knowledge gaps are identified which require further research in order to direct better care for the future.

The complete European guidelines on phenylketonuria: diagnosis and treatment

https://zenodo.org/record/1259489/files/article.pdf

Phenylketonuria Scientific Review Conference: state of the science and future research needs.

Recommendations for the nutrition management of phenylalanine hydroxylase deficiency

Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence.

Phenylketonuria (PKU) is caused by deficient activity of the enzyme phenylalanine hydroxylase, needed to convert the essential amino acid (AA) phenylalanine (phe) to tyrosine. In order to prevent neurological damage, lifelong adherence to a low-phe diet that is restricted in natural foods and requires ingestion of a phe-free AA formula to meet protein needs is required. The goal of nutritional management for those with PKU is to maintain plasma phe concentrations that support optimal growth, development, and mental functioning while providing a nutritionally complete diet. This paper reviews developing a lifelong dietary prescription for those with PKU, outcomes of nutritional management, compliance with the low-phe diet across the life cycle, and new options for nutritional management. An individualized dietary prescription is needed to meet nutrient requirements, and the adequacy of phe intake is monitored with assessment of blood phe levels. Elevated phe concentrations may occur due to illness, excessive or inadequate phe intake, or inadequate intake of AA formula. Although normal growth and development occurs with adherence to the low-phe diet, it is important to monitor vitamin, mineral and essential fatty acid status, especially in those who do not consume sufficient AA formula. Given the growing population of adults with PKU, further research is needed to understand the risks for developing osteoporosis and cardiovascular disease. There are promising new options to liberalize the diet and improve metabolic control such as tetrahydrobiopterin therapy or supplementation with large neutral AAs. Moreover, foods made with glycomacropeptide, an intact protein that contains minimal phe, improves the PKU diet by offering a palatable alternative to AA formula. In summary, continued efforts are needed to overcome the biggest challenge to living with PKU - lifelong adherence to the low-phe diet.

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Nutritional Management of Phenylketonuria

Treatment of phenylketonuria (PKU, OMIM 261600) means a diet restricted in natural protein and supplemented with phenylalanine (Phe)-free l-amino acid mixtures. Growth impairment has been described even in patients with a total protein intake at or above the recommended dietary allowance (RDA). In the present study, growth and body composition (fat-free mass (FFM) and fat) were recorded over 12 months in 34 treated PKU patients (mean age 8.7 years at baseline). Measurements were compared with those of healthy peers and with general population standard (Z-) scores calculated using the LMS method. In 28 PKU patients, data on birth weight and birth length were available and related to measurements at baseline of the study. Mean total protein intake in PKU patients was 124% (range 77–193%) of the RDA (DACH 2000). No significant differences in growth and body composition were present between PKU patients and healthy populations either at birth or during the study period. The significant correlation of FFM (representing muscle mass) with intake of natural protein—rather than total protein—indicates that the enhancement of tolerance to natural protein may be of value in PKU patients.

D. Möslinger

Papers

Growth and body composition in children with classical phenylketonuria: results in 34 patients and review of the literature.