Tetrahydrobiopterin: Potential Role in Treatment of Phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive metabolic disease caused by a genetic mutation that inhibits the conversion of the amino acid phenylalanine (Phe) into tyrosine. PKU diagnosis is based on detection of high concentrations of Phe in the blood serum. When blood levels of Phe are too high (hyperphenylalaninemia), the condition is toxic and could lead to mental retardation, epilepsy or other neurological abnormalities. Some patients diagnosed with PKU are also defective in the production of or lack the ability to produce tetrahydrobiopterin (BH4) due to a genetic defect. BH4 is the cofactor for the enzyme phenylalanine hydroxylase (PAH), which catalyzes Phe into tyrosine. Previously, the preferred treatment of PKU was a strict diet limiting Phe. The purpose of this literature research project is to investigate an alternative therapy for the regulation of Phe levels for patients with PKU by investigating the clinical relevance of BH4 administration. This project summarizes the effects and benefits of administering BH4 to patients with PKU to initiate the break down of Phe into tyrosine. Many patients find it extremely difficult to follow such strict diets to eliminate Phe, so the option of BH4 administration is very appealing. If patients are permitted a moderate amount Phe in their diet and given medication (BH4) to regulate blood Phe levels, they are more likely to follow a therapy regimen when compared to strictly limiting or completely omitting Phe from their diet. Compliance with therapy will increase the overall health of a PKU patient