Phenylketonuria (also known as Phenylalanine hydroxylase deficiency, and PKU) is an inborn error of metabolism involving impaired metabolism of the amino acid phenylalanine. Phenylketonuria is caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity. The condition is also known as phenylalanine hydroxylase deficiency.
Protein-rich foods or the sweetener aspartame can act as poisons for people with phenylketonuria. The role of PAH is to break down excess phenylalanine from food. Phenylalanine is a necessary part of the human diet and is naturally present in all kinds of dietary protein. It is also used to make aspartame, known by the trade name Nutrasweet, which is used to sweeten low-calorie and sugar free soft drinks, yogurts, and desserts. In people without PKU, the PAH enzyme breaks down any excess phenylalanine from these sources beyond what is needed by the body. However, if there is not enough of the PAH enzyme or its cofactor, then phenylalanine can build up in the blood and brain to toxic levels, affecting brain development and function. PKU is rare, but important to identify, because if caught early it is very treatable. It is not contagious, and it is lifelong, but with early diagnosis and consistent treatment, the damaging effects can be minimal or non-existent.
Untreated PKU can lead to intellectual disability, seizures, and other serious medical problems. The best proven treatment for classical PKU patients is a strict phenylalanine-restricted diet supplemented by a medical formula containing amino acids and other nutrients. In the United States, the current recommendation is that the PKU diet should be maintained for life. Patients who are diagnosed early and maintain a strict diet can have a normal life span with normal mental development.
PKU is an inherited disease. When an infant is diagnosed with PKU, it is never the result of any action of the parents or any environmental factor. Rather, for a child to inherit PKU, both of his or her parents must have at least one mutated allele of the PAH gene. Most parents who are carriers of PKU genes are not aware that they have this mutation because being a carrier causes no medical problems. To be affected by PKU, a child must inherit two mutated alleles, one from each parent.