Problems in Prenatal Diagnosis Using Sphingolipid Hydrolase Assays

  • J. Alexander Lowden
  • Marie-Anne LaRamee
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 19)


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.


Amniotic Fluid Prenatal Diagnosis Human Spleen Sphingomyelinase Activity Lipid Storage Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Crocker, A.C. The cerebral defect in Tay-Sachs disease and Niemann-Pick disease. J. Neurochem. 7: 69, (1961).PubMedCrossRefGoogle Scholar
  2. 2.
    Brady, R.O., Kanfer, J.N., Mock, M.B. and Fredrickson, D.S. The metabolism of sphingomyelin, II. Evidence of an enzymatic deficiency in Niemann-Pick disease. Proc. Nat. Acad. Sci. U.S.A. 55: 366, (1966).CrossRefGoogle Scholar
  3. 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. 4.
    Lowden, J.A. and LaRamee, M.A. Sphingomyelinase in Type C Niemann-Pick disease. Arch. Neurol. Submitted, October 1971.Google Scholar
  5. 5.
    Spence, M.W. personal communication.Google Scholar
  6. 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. 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
  8. 8.
    Crocker, A.C. and Farber, S. Niemann-Pick Disease: A review of eighteen patients. Medicine 37: 1, (1958).PubMedCrossRefGoogle Scholar
  9. 9.
    Derry, D.M., Fawcett, J.S., Andermann, F. and Wolfe, L.S. Late infantile systemic lipidosis. Major monosialogangliosidosis, delineation of two types. Neurology 18: 340, (1968).PubMedCrossRefGoogle Scholar
  10. 10.
    Lowden, J.A., Olivares, R., and Reilly, B.J. Infantile GM1 gangliosidosis. Arch. Neurol. Submitted, October 1971.Google Scholar
  11. 11.
    Wolfe, L.S., Callahan, J., Fawcett, J.S., Andermann, F. and Scriver, C.R. GMl-gangliosidosis without chondrodystrophy or visceromegaly: Beta-galactosidase deficiency with gangliosidosis and the excessive excretion of a keratan sulfate. Neurology 20: 23, (1970).PubMedCrossRefGoogle Scholar
  12. 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
  13. 13.
    Pinsky, L. and Powell, E. GM1-gangliosidosis Types 1 and 2: Enzymatic differences in cultured fibroblasts. Nature 228: 1093, (1970).PubMedCrossRefGoogle Scholar
  14. 14.
    Okada, S. and O’Brien, J.S. Tay-Sachs Disease: Generalized absence of a Beta-D-N-Acetylhexosaminidase component. Science 165: 698, (1969).PubMedCrossRefGoogle Scholar
  15. 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
  16. 16.
    Walker, P.G., Woollen, M.E. and Pugh, D. N-acetyl-β-glucosa minidase activity in serum during pregnancy. J. Clin. Path. 13: 353, (1960).PubMedCrossRefGoogle Scholar
  17. 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
  18. 18.
    O’Brien, J.S., Okada, S., Fillerup, D.L., Veath, M.L. Adornato, B., Benner, P.H. and Leroy, J.G. Tay-Sachs disease: Prenatal diagnosis. Science 172: 61, (1971).PubMedCrossRefGoogle Scholar
  19. 19.
    Frohwein, Y.Z. and Gatt, S. Isolation of β-N-Acetylhexosaminidase, β-N-Acetylglucosa minidase, and ß-N-Acetylgalactosaminidase from calf brain. Biochem. 6: 2775, (1967).CrossRefGoogle Scholar
  20. 20.
    Robinson, D. and Stirling, J.L. N-Acetyl-β-glucosaminidases in human spleen. Biochem. J. 107: 321, (1968).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1972

Authors and Affiliations

  • J. Alexander Lowden
    • 1
  • Marie-Anne LaRamee
    • 1
  1. 1.Research InstituteThe Hospital for Sick ChildrenTorontoCanada

Personalised recommendations