TETRAHYDROBIOPTERIN AND INHERITED HYPERPHENYLALANINEMIAS

Tetratrydrobiopterin deficiency, a variant of hyperphenylalaninemia, m ay be caused by deficiency of one of the following enzymes: guanosine triphosphate cyclohydrolase 1, 6-pyruvoyltetrahydropterin synthase, di hydropteridin reductase and pterin-4a-carbinolamine dehydratase. The f irst two enzymes are involved in the biosynthesis of tetrahydrobiopter in, the last two in its regeneration. Although these diseases are rare , early detection by selective screening is essential for the treatmen t and outcome, Tetrahydrobiopterin deficiencies are very heterogenous ranging from mild forms requiring only marginal if any treatment to se vere forms which are in some cases very difficult to treat. All varian ts of tetrahydrobiopterin deficiency can be differentiated from the cl assical phenylketonuria (PKU) by measurement of pterin metabolites in patients' urine, tetrahydrobiopterin loading test, and by dihydropteri dine reductase activity in erythrocytes from the Guthrie card.