Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine.Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders.Phenylketonuria is an inherited genetic disorder. It is caused by mutations in the PAH gene, which can result in inefficient or nonfunctional phenylalanine hydroxylase, an enzyme responsible for the metabolism of excess phenylalanine.This results in the buildup of dietary phenylalanine to potentially toxic levels.It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop.There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains.Those with one copy of a mutated gene typically do not have symptoms.[1] Many countries have newborn screening programs for the disease.
PKU is an autosomal recessive metabolic genetic disorder. As an autosomal recessive disorder, two PKU alleles are required for an individual to experience symptoms of the disease. For a child to inherit PKU, both parents must have and pass on the defective gene. If both parents are carriers for PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will be a carrier and a 25% chance the child will neither develop nor be a carrier for the disease.[5]

PKU is characterized by homozygous or compound heterozygous mutations in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.[18]: 541  This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine (Tyr). When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which can be detected in the urine