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

Key European guidelines for the diagnosis and management of patients with phenylketonuria

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive inborn error of phenylanaline metabolism. PKU is characterized by deficient or defective phenylalanine hydroxylase activity and persistantly increased levels of the essential amino acid phenylalanine in the circulation. The present article examines current understanding of the etiology of PKU, along with a meta-analysis examining neuropsychological and intellectual presentations in continuously treated adolescents and adults. Patients with PKU differed significantly from controls on Full-Scale IQ, processing speed, attention, inhibition, and motor control. Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient.

D. Whittle

Papers

Magnetic resonance imaging of the brain in phenylketonuria