Phenylalanine hydroxylase deficiency

Phenylalanine hydroxylase deficiency: diagnosis and management guideline.

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.

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

Objective: Several studies have suggested a compromised bone mass in phenylketonuria patients but most reported on heterogeneous or small patient groups Our aim was to evaluate peak bone mass in adult PKU patients and to relate BMD to nutritional parameters Patients and methods: BMD was measured by dual-energy x-ray absorptiometry in 31 adult PKU patients (18 female), mean age 25 ± 53 years Nutritional intake was calculated based on food diaries Diet adherence was determined based on patients’ report Results: Mean blood phenylalanine (Phe) concentration was 968 ± 526 μmol/L (16 ± 87 mg/dl) Eight patients (322%) met the recommended blood Phe concentration of <726 μmol/L (<12 mg/dl), and there was no significant difference in Phe concentrations between diet-adherent and non-adherent patients Osteopenia was detected in 11 patients (387%), while osteoporosis was detected in 2 patients (65%) No correlation was found between BMD and age, blood minerals, Phe, vitamin D and alkaline phosphatase levels, calcium and protein intake, body mass index, and body fat percentage Conclusions: Peak bone mass is decreased in PKU patients Possible explanations include long-standing dietary deficiency in protein, calcium, vitamin D or trace elements, or a primary defect in bone turnover inherent to the disease itself Our data do not favour any of these hypotheses Further studies are needed to elucidate the cause of low bone density in PKU patients

I. Vered

Papers

Peak bone mass in patients with phenylketonuria