Phenylketonuria

Article By:

de la Cruz, Felix Intellectual and Developmental Disabilities Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Last reviewed:January 2021

DOI:https://doi.org/10.1036/1097-8542.506900

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• Phenylketonuria, published June 2014:Download PDF Get Adobe Acrobat Reader

An inborn error of metabolism in which affected individuals lack the enzyme phenylalanine hydroxylase, which is needed to metabolize phenylalanine (an amino acid essential for normal growth and development). Phenylketonuria (PKU) is a rare inherited metabolic disorder that causes increased levels of the amino acid phenylalanine (which is necessary for normal growth and development) in the blood. The disorder results from mutations in the gene that regulates the liver enzyme phenylalanine hydroxylase (PAH) [see illustration], which converts phenylalanine into tyrosine. Thus, persons with phenylketonuria have a deficiency in PAH. If untreated, affected individuals may suffer from severe intellectual disability, become microcephalic (having a smaller-than-normal brain), have behavioral problems, develop epilepsy, or show other signs of neurological impairment. Phenylketonuria is inherited as an autosomal recessive trait and is found in all ethnic groups, but most frequently in individuals of northern European descent. Its incidence is about 1 in 10,000–20,000 births, depending on the country of origin. Classically, persons with phenylketonuria exhibit blood phen­ylalanine concentrations of 20 mg/deciliter or more (normal concentrations are about 1–2 mg/deciliter), normal blood tyrosine levels, and excessive phenylalanine metabolites in the urine while on a normal diet. Phenylketonuria variants have blood phenylalanine concentrations of 10–20 mg/deciliter, but may not have phenylalanine metabolites in their urine unless they have ingested excessive amounts of proteins. See also: Amino acid; Enzyme; Gene; Intellectual disability; Metabolic disorders; Metabolism; Mutation

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