Phenylketonuria

Phenylketonuria

Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934.

Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder characterizedby a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the aminoacid tyrosine (Tyr). When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine.

Classical PKU iscaused by a mutated gene for the enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine to other essential compounds in the body. Other non-PAH mutations can also cause PKU.This is an example of genetic heterogeneity.
PKU is known to be an autosomal recessive genetic disorder. This means both parents must have at least one mutated allele of the PAH gene. The child mustinherit both mutated alleles, one from each parent. 

If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but only by managing and controlling (Phe)levels through diet, or a combination of diet and medication. 
When left untreated, complications of PKU include:
* Severe mental retardation
* Brain function abnormalities
* Microcephaly* Mood disorders
* Irregular motor functioning
* Behavioral problems such as ADHD.
Supplementary infant formulas. The oral administration of tetrahydrobiopterin (or BH4) (a cofactor forthe oxidation of phenylalanine) can reduce blood levels of this amino acid in certain patients.
Several other therapies are currently under investigation, including gene therapy, large neutral aminoacids, and enzyme substitution therapy with phenylalanine ammonia lyase (PAL).

The mean incidence of PKU varies widely in different human populations. In Turkey, 1 in 2600 births (the highest rate...