Last reviewed: 29 Dec 2022
Last updated: 28 Sep 2018



History and exam

Key diagnostic factors

  • family history of PKU
  • positive newborn screen for PKU
More key diagnostic factors

Other diagnostic factors

  • intellectual disability
  • microcephaly
  • eczema
  • light pigmentation of eyes and hair
  • seizures
  • mousy odour of urine
Other diagnostic factors

Risk factors

  • family history of PKU
  • white ancestry
More risk factors

Diagnostic investigations

1st investigations to order

  • newborn screening for metabolic disorders
More 1st investigations to order

Investigations to consider

  • quantitative plasma amino acid analysis
  • blood dihydropteridine reductase (DHPR) assay
  • urine neopterin to biopterin ratio
  • mutation analysis of phenylalanine hydroxylase gene
  • tetrahydrobiopterin (BH4)-responsiveness test
More investigations to consider

Treatment algorithm


all patients



Barbara K. Burton, MD

Professor of Pediatrics

Northwestern University Feinberg School of Medicine


PKU Clinic

Ann and Robert H. Lurie Children’s Hospital of Chicago




BKB has received consulting fees and funding for the conduct of clinical trials from BioMarin Pharmaceutical, the manufacturer of sapropterin and pegvaliase (pegylated phenylalanine ammonia-lyase).

Peer reviewers

Harvey L. Levy, MD

Senior Physician in Medicine/Genetics

Children's Hospital Boston

Professor of Pediatrics

Harvard Medical School




HLL has served on the PKU Scientific Advisory Board for BioMarin Pharmaceuticals Inc. and has received consultation fees from the company for attending meetings, giving lectures, and participating in symposia. BioMarin markets treatment for phenylketonuria.

Berthold Koletzko, MD

Professor of Pediatrics

University of Munich

Head of Division of Metabolic Diseases and Nutritional Medicine

Dr von Hauner Children's Hospital

Ludwig-Maximilians-University of Munich




BK has received research support from Danone Medical Nutrition and is the recipient of a Freedom to Discover Award of the Bristol Myers Squibb Foundation.

  • Differentials

    • Inborn errors of tetrahydrobiopterin (BH4) synthesis
    • Hepatic dysfunction
    • Extreme prematurity
    More Differentials
  • Guidelines

    • The complete European guidelines on phenylketonuria: diagnosis and treatment
    • Management of PKU
    More Guidelines
  • Patient leaflets

    ADHD: what is it?

    ADHD in children: what treatments work?

    More Patient leaflets
  • padlock-lockedLog in or subscribe to access all of BMJ Best Practice

Use of this content is subject to our disclaimer