Phenylketonuria (PKU) was one of the first inherited metabolic diseases to be tested for in newborns. PKU is a rare enzyme deficiency; only about 250 babies are born with this condition in the United States each year.
It is important to test for PKU because if it is not detected at birth, the enzyme deficiency will cause an entirely preventable form of mental retardation. An infant who inherits two copies of a mutation in the phenylalanine hydroxylase (PAH) gene cannot metabolize the amino acid phenylalanine found in proteins. With a normal diet, the phenylalanine level rises too high, and the baby develops brain damage and mental retardation.
Children with PKU who are given a strict low-phenylalanine diet from infancy will not develop brain damage. Common foods that contain phenylalanine include milk and eggs. The artificial sweetener NutraSweet (aspartame) contains phenylalanine, so food and drinks that use this sweetener are also banned from the PKU diet.
A woman with PKU who is or wants to become pregnant must be especially careful to follow a low-phenylalanine diet in order to avoid problems for the developing fetus.
For the full list of PKU-associated mutations in the PAH gene as of August 2016, curated based on the criteria listed below, see the following Table:
Mutations were considered pathogenic for phenylketonuria based on being listed as pathogenic in ClinVar and/or having an Assigned Value (AV) or Allelic Phenotype Value (APV) of less than 2 in the BioPKU PAHvdb database. Most mutations listed lead (when recessively inherited) to the classic PKU phenotype, however a few leading to somewhat milder phenotypes are included, for example when multiple ClinVar submitters consider the mutation pathogenic.