Phenylketonuria (PKU) is a rare inborn error of metabolism associated with elevated blood phenylalanine. Clinical features in the untreated patient include intellectual disability, seizures, and eczema.
Early treated patients typically have normal intellectual development with an IQ within the normal range, although subtle neurocognitive deficits are observed and there is an increased incidence of attention deficit disorder, executive functioning deficits, and mental health concerns.
Caused by a deficiency of hepatic phenylalanine hydroxylase activity. Gene mutations are biallelic, most often compound heterozygous, 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 multidisciplinary team of specialists.
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. Pegvaliase is a newer option that can allow for a regular diet.
Phenylketonuria (PKU) is an autosomal-recessive inborn error of amino acid metabolism characterized by elevated (typically >6 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 hyperphenylalaninemia (hyperphe). Both disorders are the result of mutations in the gene for phenylalanine hydroxylase, 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 odor 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 or recycling
- Hepatic dysfunction
- Extreme prematurity
- The complete European guidelines on phenylketonuria: diagnosis and treatment
- Phenylalanine hydroxylase deficiency: diagnosis and management guideline
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