169 ELEVEN YEARS OF SCREENING ON TETRAHYDROBIOPTERIN DEFICIENCY: THE ZURICH EXPERIENCE

Abstract

Tetrahydrobiopterin (BH4) deficiency comprises a group of very rare diseases characterized by progressive neurological symptoms unresponsive to treatment with low-phenylalanine diet. 6-Pyruvoyl-tetrahydropterin synthase deficiency, the most common form of BH4 deficiency, occurs in various clinical forms which are sometimes hard to distinguish. This complicates the screening of newborns, prenatal diagnosis, and the determination of heterozygote carriers. Beside the severe, the peripheral, and the transient forms there might be other variants only marginally characterized. In dihydropteridine reductase deficiency, the second most common form of BH4 deficiency, various point mutations have been observed. Recently a new form of hyperphenylalaninemia, primapterinuria, with excretion of 7-substituted pterins in urine was described. This form of hyperphenylalaninemia may be due to carbanolamine dehydratase deficiency. As a result of the Central European screening carried out in our laboratory during the last 11 years approx. 1300 patients with hyperphenylalaninemia have been tested, of which 970 are newborns. 79 patients with BH4 deficiency were discovered. Of these 79 patients 2 suffer from GTP cyclohydrolase I deficiency, 48 from 6-pyruvoyl-tetrahydropterin synthase deficiency (5 with a peripheral defect), 22 from dihydropteridine reductase deficiency, and 7 from primapterinuria.