Prenatal diagnosis of Gaucher's and Niemann-Pick diseases. Assays of glucocerebrosidase and sphingomyelinase in tissue cultures using natural substrates

Abstract

Prenatal diagnosis has been successfully achieved by enzyme assays in cultured amniocytes in three high risk pregnancies for Gaucher's disease and three for Niemann-Pick disease type A. [14C]Stearic acid glucocerebroside and [3H]-dihydrosphingomyelin were used as substrates for glucocerebrosidase and sphingomyelinase activity measurements, respectively. Values for the above two enzyme levels in cultured amniotic fluid cells of normal controls and in the pregnancies at risk are presented. The diagnosis made in utero in one fetus affected with Niemann-Pick disease was subsequently confirmed following abortion (at 19 weeks gestation), by the specific biochemical and pathological features of various organs of the afflicted fetus (to be published). Confirmation of diagnoses made in utero for heterozygous and healthy fetuses was obtained by post-partum examination of glucocerebrosidase and spingomyelinase activity levels in leukocytes of the appropriate infants.