First trimester prenatal diagnosis of Tay-Sachs disease using the sulfated synthetic substrate for hexosaminidase A.

Uncultured and cultured embryonic trophoblastic tissue obtained by chorionic villus sampling (CVS) displays enzyme activity towards 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranosyl-6-sulfate (MUGS), a specific substrate for Hexosaminidase A (Hex A), the enzyme deficient in Tay-Sachs disease (TSD). Specific activity is comparable to that found in cultured amniocytes and fibroblasts. The enzyme activity has a pH optimum of 4.1 and an apparent Km of 6 x 10(-4) mol/L. Thirteen pregnancies in eight families at risk for TSD were monitored by CVS using MUGS as the Hex A substrate. Four fetuses were proven affected by enzyme analysis of fetal tissues and cultured fetal fibroblasts obtained at the time of termination of the pregnancies. Nine fetuses were judged to be unaffected. Eight babies were clinically normal while the other pregnancy is continuing. The use of MUGS as substrate for Hex A makes prenatal diagnosis by CVS of families at risk for TSD simple, direct and accurate.