A rare inborn error of metabolism associated with elevated blood phenylalanine. Clinical features in the untreated patient include intellectual disability, defects in executive functioning, seizures, and eczema.
Caused by a deficiency of hepatic phenylalanine hydroxylase activity. Gene mutations are heterogeneous, and therefore residual enzyme activity and blood phenylalanine levels are variable and correlate with the severity of the disorder.
Diagnosed by newborn screening and managed by a multi-disciplinary team of specialists.
Treated patients have an IQ within the normal range, although subtle neurocognitive deficits are observed and there is an increased incidence of attention deficit disorder and failure to do well at school.
Treatment for most patients involves restriction of dietary protein and phenylalanine, and supplementation with phenylalanine-free amino acid mixtures. Tetrahydrobiopterin (BH4)-responsive patients may also be treated with sapropterin.
Phenylketonuria (PKU) is an autosomal-recessive inborn error of amino acid metabolism characterised by elevated (typically >605 micromol/L [10 mg/dL]) blood phenylalanine (phe), which, if untreated, results in intellectual disability, seizures, and eczema. Patients with elevated blood phe below the threshold requiring treatment are referred to as having hyper-phenylalaninaemia (hyper-phe). Both disorders are the result of mutations in the gene for phenylalanine hydroxylase (PAH), and represent a spectrum of severity.
History and exam
Key diagnostic factors
- family history of PKU
- positive newborn screen for PKU
Other diagnostic factors
- intellectual disability
- light pigmentation of eyes and hair
- mousy odour of urine
- family history of PKU
- white ancestry
1st investigations to order
- newborn screening for metabolic disorders
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
- Inborn errors of tetrahydrobiopterin (BH4) synthesis
- Hepatic dysfunction
- Extreme prematurity
- The complete European guidelines on phenylketonuria: diagnosis and treatment
- Management of PKU
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