Phenylketonuria

Phenylketonuria (PKU) is a rare inborn error of metabolism associated with elevated blood phenylalanine. Clinical features in untreated patients 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 multi-disciplinary 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, which may allow for a less restrictive diet in some people. Pegvaliase, an enzyme substitution therapy, is a treatment option for adolescents and adults with PKU that can allow for a regular diet.

PKU is an autosomal-recessive inborn error of amino acid metabolism characterised by elevated (typically >363 micromol/L [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 hyper-phenylalaninaemia (hyper-phe). Both disorders are the result of mutations in the gene for phenylalanine hydroxylase, and represent a spectrum of severity.