PRENATAL-DIAGNOSIS OF SANFILIPPO A SYNDROME - EXPERIENCE IN 35 PREGNANCIES AT RISK AND THE USE OF A NEW FLUOROGENIC SUBSTRATE FOR THE HEPARIN SULFAMIDASE ASSAY

We have investigated the use of a 4-methylumbelliferone (MU) derived a rtificial substrate, MU-alpha-D-N-sulphoglucosaminide, for the sulpham idase assay in chorionic villi and amniotic fluid cells. In the new tw o-step enzyme assay, fluorescent MU is released by the successive acti on of endogenous sulphamidase and an added yeast enzyme preparation wh ich hydrolyses the MU-alpha-glucosaminide intermediate. Optimal condit ions for a sensitive, accurate, and convenient procedure for use in th e prenatal diagnosis of Sanfilippo A syndrome are described. Previousl y, prenatal diagnosis of Sanfilippo A syndrome has been achieved by a radioactive sulphamidase assay in chorionic villi or in cultured amnio cytes and by two-dimensional electrophoresis of glycosaminoglycans in amniotic fluid. Our experience using these methods in 35 pregnancies a t risk is reported. The feasibility of the new fluorogenic assay was e valuated by retrospective testing of stored homogenates of chorionic v illi and amniotic fluid cells from 22 pregnancies at risk. Unequivocal assignment of the fetal status in five affected pregnancies and 17 pr egnancies with a normal outcome confirms the reliability of the new su lphamidase assay, which is in every respect more convenient than the c onventional method using S-35-radiolabelled heparin.