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Last reviewed: 4 Sep 2023
Last updated: 14 Feb 2023



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 odor 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 honoraria from Biomarin for speaking engagements. She has conducted contract research funded by Biomarin and Homology Medicines.

Peer reviewers

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.

Stephanie Sacharow, MD

Medical Geneticist

Division of Genetics and Genomics

Boston Children's Hospital




SS has participated on advisory boards and has given talks at conferences sponsored by Biomarin. She has been a principal investigator in studies with Biomarin, Synlogic, and PTC Therapeutics.

  • Differentials

    • Inborn errors of tetrahydrobiopterin or recycling
    • Hepatic dysfunction
    • Extreme prematurity
    More Differentials
  • Guidelines

    • The complete European guidelines on phenylketonuria: diagnosis and treatment
    • Phenylalanine hydroxylase deficiency: diagnosis and management guideline
    More Guidelines
  • Patient leaflets

    ADHD: what is it?

    ADHD: questions to ask your doctor

    More Patient leaflets
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