Summary
Definition
History and exam
Key diagnostic factors
- family history of phenylketonuria (PKU)
- positive newborn screen for phenylketonuria
Other diagnostic factors
- intellectual disability
- microcephaly
- eczema
- light pigmentation of eyes and hair
- seizures
- mousy odor of urine
Risk factors
- family history of phenylketonuria (PKU)
- white ancestry
Diagnostic tests
1st tests to order
- newborn screening for metabolic disorders
Tests 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
Treatment algorithm
all patients
Contributors
Authors
Barbara K. Burton, MD
Professor of Pediatrics
Northwestern University Feinberg School of Medicine
Director
PKU Clinic
Ann and Robert H. Lurie Children’s Hospital of Chicago
Chicago
IL
Disclosures
BKB has received consulting fees from Biomarin, PTC Therapeutics, and Jnana.
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
Lindwurmstr
Germany
Disclosures
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
Boston
MA
Disclosures
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.
References
Key articles
National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication].Full text
Smith WE, Berry SA, Bloom K, et al. Phenylalanine hydroxylase deficiency diagnosis and management: a 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jan;27(1):101289.Full text Abstract
van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017 Oct 12;12(1):162.Full text Abstract
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Differentials
- Inborn errors of tetrahydrobiopterin or recycling
- Hepatic dysfunction
- Extreme prematurity
More DifferentialsGuidelines
- Phenylalanine hydroxylase deficiency diagnosis and management
- PKU nutrition management guidelines
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