ANTENATAL DIAGNOSIS OF TETRAHYDROBIOPTERIN DEFICIENCY BY QUANTIFICATION OF PTERINS IN AMNIOTIC-FLUID AND ENZYME-ACTIVITY IN FETAL AND EXTRAFETAL TISSUE

Prenatal diagnosis of tetrahydrobiopterin (BH4) deficiency was underta ken by evaluating the pterin patterns in amniotic fluid and the specif ic enzyme activities in fetal or extrafetal tissues. This allowed the prenatal diagnosis in 19 pregnancies at risk. In 8 families with a chi ld already affected by dihydropteridine reductase deficiency 4 fetuses were diagnosed as homozygotes and 4 as heterozygotes for the defect. In 11 families with a child affected by 6-pyruvoyl tetrahydropterin sy nthase deficiency 4 fetuses were homozygous, 4 heterozygous and 3 norm al. This study also advanced our knowledge of tetrahydrobiopterin meta bolism during fetal development. The key enzymes involved in the biosy nthesis of BH4 are expressed early and allow the fetus to be autotroph us for its cofactor requirement. In a twin pregnancy, both fetuses wer e diagnosed to be heterozygotes for dihyeropterine reductase deficienc y and primapterin (7-biopterin) in amniotic fluid was increased. This indicates that pterin-4 alpha-carbinolamine dehydratase activity seems to be differently expressed during fetal life. As a consequence, pter ins detected in amniotic fluid are of fetal origin and 6- and 7-substi tuted pterins can be present in amniotic fluid in higher proportions w hen compared with other body fluids.