Problems in Prenatal Diagnosis Using Sphingolipid Hydrolase Assays
When Dr. Volk asked for my title last spring I thought that a rather mundane study of changes in sphingolipid hydrolase activity during growth and development would demonstrate some points about sphingolipid turnover. We wanted to know why certain organs store particular sphingolipids although they apparently have adequate levels of enzyme activity. During the interim several unrelated bits of information have stimulated a change in this plan. I am becoming concerned about our rapid advance into the service approach to prenatal diagnosis using assays of enzyme activity in amniotic fluid as well as in cultured amniocytes. It is certainly true that the feasibility of monitoring pregnancies in high-risk families is the most hopeful and important development in the history of sphingolipid biology. I want to discuss, today, some of the dangers inherent in our as yet early knowledge. I am worried that we may think we know more than we really do and in our ignorance we may make wrong decisions which can feasibly destroy the credibility of the entire programme. I shall talk today only about sphingomyelinase, β-galactosidase and hexosaminidase but the problems mentioned probably apply equally to many other hydrolases.
KeywordsAmniotic Fluid Prenatal Diagnosis Human Spleen Sphingomyelinase Activity Lipid Storage Disease
Unable to display preview. Download preview PDF.
- 3.Schneider, R.B. and Kennedy, E.P. Sphingomyelinase in normal human spleens from subjects with Niemann-Pick disease. J. Lip. Res. 8: 202, (1967).Google Scholar
- 4.Lowden, J.A. and LaRamee, M.A. Sphingomyelinase in Type C Niemann-Pick disease. Arch. Neurol. Submitted, October 1971.Google Scholar
- 5.Spence, M.W. personal communication.Google Scholar
- 6.Schneider, E.L., Ellis, W.G., Brady, R.O., McCulloch, J.R. and Epstein, C.J. Prenatal Niemann-Pick disease: Biochemical and histological examination of a 19 gestational week fetus. Submitted for publication, September 1971.Google Scholar
- 7.Fredrickson, D.S. in The Metabolic Basis of Inherited Disease. Stanbury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. eds. New York, McGraw-Hill, 1966, p. 586.Google Scholar
- 10.Lowden, J.A., Olivares, R., and Reilly, B.J. Infantile GM1 gangliosidosis. Arch. Neurol. Submitted, October 1971.Google Scholar
- 12.O’Brien, J.S., Okada, S., Ho, M.W., Fillerup, D.L., Veath, M.L. and Adams, K. in Lipid Storage Diseases. Enzymatic and clinical implications. Bernsohn, J. and Grossman, H.J. eds. New York, Acad. Press, 1971, p. 225.Google Scholar
- 15.O’Brien, J.S., Okada, S., Chen, A. and Fillerup, D.L. Tay-Sachs disease. Detection by serum hexosaminidase assay. New Eng. J. Med. 283: 15, (1970).Google Scholar
- 17.Schneck, L., Valenti, C., Amsterdam, D., Freidland, J., Adachi, M., and Volk, B.W. Prenatal diagnosis of Tay-Sachs disease. Lancet I: 582, (1970).Google Scholar