Summary

• A rare inborn error of metabolism associated with elevated blood phenylalanine. Clinical features in the untreated patient include mental retardation, 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.