Phenylketonuria

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 multidisciplinary 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 characterized by elevated (typically >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 hyperphenylalaninemia (hyperphe). Both disorders are the result of mutations in the gene for phenylalanine hydroxylase (PAH), and represent a spectrum of severity.