Phenylketonuria

Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of phenylalanine. Phenylalanine is one of the building blocks (amino acids) of proteins. Humans cannot make phenyalanine, but it is a natural part of the foods we eat. However, people do not need all the phenyalanine they eat, so the body converts extra phenylalanine to another harmless amino acid, tyrosine. People with PKU cannot properly break down the extra phenylalanine to convert it to tyrosine. This means phenylalanine builds up in the person's blood, urine, and body. If PKU is not treated, phenylalanine can build up to harmful levels in the body.

PKU varies from mild to severe. The most severe form is known as classic PKU. Without treatment, children with classic PKU develop permanent intellectual disability. Light skin and hair, seizures, developmental delays, behavioral problems, and psychiatric disorders are also common. Less severe forms, sometimes called "mild PKU", "variant PKU" and "non-PKU hyperphenylalaninemia", have a smaller risk of brain damage. Mothers who have PKU and no longer follow a phenylalanine-restricted diet have an increased risk of having children with an intellectual disability, because their children may be exposed to very high levels of phenylalanine before birth.

In most cases, PKU is caused by changes (pathogenic variants, also called mutations ) in the PAH gene. Inheritance is autosomal recessive manner. Because PKU can be detected by a simple blood test and is treatable, PKU is part of newborn screening. Treatment for PKU normally involves a phenyalanine-restricted diet that is monitored carefully. Some children and adults with PKU may be helped by the medication sapropterin in combination with a low-phenylalanine diet. Adults with high phenylalanine levels despite treatment may be helped by the medication pegvaliase.