Antenatal diagnosis of genetic disease / edited by A.E.H. Emery.

Date:
1973
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Antenatal diagnosis of genetic disease / edited by A.E.H. Emery. Source: Wellcome Collection.

    142/192 (page 124)
    124 ANTENATAL DIAGNOSIS OF GENETIC DISEASE Tay-Sachs disease is due to a deficiency of hexosaminidase A, and Schneck, Friedland, Valenti, Adachi, Amsterdam and Volk (1970) diagnosed the disease in utero at 18 to 20 weeks gestation by demonstrating only trace amounts of enzyme activity in amniotic fluid and uncultured amniotic fluid cells. More recent experience by this group has confirmed this finding (Friedland, Perle, Saifer, Schneck and Volk, 1971). In a recent and extensive study (O'Brien, Okada, Fillerup, Veath, Adornato, Brenner and Leroy, 1971), 15 pregnant women at risk of having a child with Tay-Sachs disease were monitored by amniocentesis with hexo¬ saminidase A assays on amniotic fluid, cultured and uncultured amniotic fluid cells. The results of this study clearly demonstrated that the greatest difference in enzyme levels between normal and affected fetuses was with cultured amniotic fluid cells. In the case of uncultured cells and the fluid itself, the difference between the two groups was smaller but still clear cut with no apparent over¬ lap. The results from the assay of uncultured cells and fluid were obtained within two days after amniocentesis but results from cultured cells were obtained only after 10 to 28 days. The advan¬ tage of using fluid and uncultured cells is therefore obvious provided there is no contamination with maternal blood. There is presumably more scope for antenatal diagnosis based on enzyme assays on amniotic fluid. Normal values for a number of enzymes in amniotic fluid have been published (Geyer and Schneider, 1970) and their origin discussed (Geyer, 1970). Sutcliffe and Brock (1972) have studied the specific activities of five enzymes; acid phosphatase, heat-stable and heat-labile alkaline phosphatases, hexosaminidase and a-l,4-glucosidase in amniotic fluids obtained at various stages of gestation from 10 weeks to term. They found two major peaks of activity, one at about 15 weeks, and the other at term. Only o;-l,4-glcosidase and heat-labile alkaline phosphatase have a strong early peak, while four enzymes (the exception being o;-l,4-glucosidase) have strong late peaks. Heat-labile alkaline phosphatase is unusual in having both early and late peaks, probably reflecting its heterogeneity. The activity patterns are similar, whether results are expressed per millilitre amniotic fluid or per gram soluble protein, an impor¬ tant point when the uneven protein curve is considered (see p. 117). These are thus at least three enzyme profiles in amniotic fluid and this represents experience with only five enzymes, three of which are lysosomal. It seems obvious that more enzymes will have to be studied individually before conclusions are reached about patterns of activity and tissue origins.