Identification of Tay-Sachs Genotypes by Hexosaminidase Analysis of Urine and Tear Samples

  • Abraham Saifer
  • June Amoroso
  • Guta Perle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 68)


The absence of N-acetyl-β-D-hexosaminidase A (Hex A, EC activity in the body fluids and tissues of patients with Tay-Sachs disease (TSD) (1,2) results in the cerebral accumulation of the GM2-ganglioside [N-acetylgalactosaminyl -(N-acetylneuraminyl)-galactosylglucosyl-ceramide] (3) and is responsible for all the clinical symptoms and pathological findings in the disease (4,5). TSD is a prototype representative of many other hereditary disorders (6).


Fabry Disease Normal Pregnancy Heat Denaturation Isoenzyme Pattern Normal Pregnant Woman 


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  1. 1.
    Okada, S., and O’Brien, J.S., Tay-Sachs disease. Generalized absence of a beta-D-N-acetylhexosaminidase component. Science 165, 698 (1969).CrossRefGoogle Scholar
  2. 2.
    Sandhoff, K., Variation of β-N-acetylhexosaminidasepattern in Tay-Sachs disease. FEBS Letters 4: 351, 1969.CrossRefGoogle Scholar
  3. 3.
    Svennerholm, L., The chemical structure of normal human brain and Tay-Sachs gangliosides. Biochem. Biophys. Res. Commun. 9, 436 (1962).PubMedCrossRefGoogle Scholar
  4. 4.
    Saifer, A., and Wishnow, D.E., Disturbances of lipid metabolism and their relationship to the lipidoses. In “Handbook of Clinical Neurology”, Vol. 10, P.J. Vinken and G.W. Bruyn, Eds. North-Holland Publ. Co., Amsterdam, 1970, pp 265–324.Google Scholar
  5. 5.
    Volk, B.W., and Schneck, L., “The Gangliosidoses”. Plenum Press, New York, N.Y., 1975.CrossRefGoogle Scholar
  6. 6.
    Stanbury, J.B., Wyngaarden, J.B., and Fredrickson, D.S., “The Metabolie Basis of Inherited Disease”, 3rd ed., McGraw-Hill, New York, N.Y., 1972.Google Scholar
  7. 7.
    Aronson, S.M., and Volk, B.W., Genetic and demographic considerations concerning Tay-Sachs’ disease. In “Cerebral Sphingolipidoses”, S.M. Aronson and B.W. Volk, Eds., Academic Press, New York, N.Y., 1962, pp 375–394.Google Scholar
  8. 8.
    Lowden, J.A., Skomorowski, M.A., Henderson, F., and Kaback, M., Automated assay of hexosaminidases in serum. Clin. Chem. 19, 1345 (1973).PubMedGoogle Scholar
  9. 9.
    Saifer, A., and Perle, G., Automated determination of serum hexosaminidase A by pH inactivation for detection of Tay-Sachs disease heterozygotes. Clin. Chem. 20, 538 (1974).PubMedGoogle Scholar
  10. 10.
    Schneck, L., Friedland, J., Valenti, C., Adachi, M., Amsterdam, D., and Volk, B.W., Prenatal diagnosis of Tay-Sachs disease. Lancet 1, 582 (1970).PubMedCrossRefGoogle Scholar
  11. 11.
    Kaback, M.M., and Zeiger, R.S., Heterozygote detection in Tay-Sachs disease: A prototype community screening program for the prevention of recessive disorders. In “Sphingolipids, Sphingolipidoses and Allied Disorders”. B.W. Volk and S.M. Aronson, Eds., Plenum Press, New York, N.Y., 1972, pp 613–632.Google Scholar
  12. 12.
    O’Brien, J.S., Okada, S., Chen, A., and Fillerup, D.L., Tay-Sachs disease: Detection of heterozygotes and homozygotes by serum hexosaminidase assay. New Engl. J. Med. 283, 15 (1970).PubMedCrossRefGoogle Scholar
  13. 13.
    Stirling, J.L., Separation and characterization of N-acetyl-β-glucosaminidases A and P from meternal serum. Biochim. Biophys. Acta 271, 154 (1972).PubMedGoogle Scholar
  14. 14.
    Price, G., and Dance, N., The demonstration of multiple heat stable forms of N-acetyl-β-glucosaminidase in normal human serum. Biochim. Biophys.Acta 271, 145 (1972).PubMedGoogle Scholar
  15. 15.
    Saifer, A., Perle, G., Valenti, C., and Schneck, L., Pre-and postnatal detection of Tay-Sachs disease. A comparative study of biochemical screening methods. In “Sphingolipids, Sphingolipidoses and Allied Disorders”. B.W. Volk and S.M. Aronson, Eds. Plenum Press, New York, N.Y., 1972, pp 599–611.Google Scholar
  16. 16.
    Saifer, A., Parkhurst, G.W., and Amoroso, J., Automated differentiation and measurement of hexosaminidase isoenzymes in biological fluids and its application to pre-and postnatal detection of Tay-Sachs disease. Clin. Chem. 21, 334 (1975).PubMedGoogle Scholar
  17. 17.
    Ellis, R.B., Ikonne, J.U., and Masson, P.K., DEAE-cellulose microcolumn chromatography coupled with automated assay: Application to the resolution of N-acetyl-β-D-hexosaminidase components. Anal. Biochem. 63, 5 (1975).PubMedCrossRefGoogle Scholar
  18. 18.
    Navon, R., and Padeh, B., Urinary test for identification of Tay-Sachs genotypes. J. Pediat. 80, 1026 (1972).PubMedCrossRefGoogle Scholar
  19. 19.
    Carmody, P.J., Rattazzi, M.C., and Davidson, R.G., Tay-Sachs disease-the use of tears for the detection of heterozygotes. New Engl. J. Med. 289, 1072 (1973).PubMedCrossRefGoogle Scholar
  20. 20.
    Saifer, A., and Rosenthal, A.L., Rapid test for the detection of Tay-Sachs disease heterozygotes and homozygotes by serum hexosaminidase assay. Clin.Chim. Acta 43, 417 (1973).CrossRefGoogle Scholar
  21. 21.
    Friedland, J., Schneck, L., Saifer, A., Pourfar, M., and Volk, B.W., Identification of Tay-Sachs disease carriers by acrylamide gel electrophoresis. Clin. Chim. Acta 28, 397 (1970).CrossRefGoogle Scholar
  22. 22.
    Padeh, B., and Navon, R., Diagnosis of Tay-Sachs disease by hexosaminidase activity in leukocytes and amniotic cells. Isr. J. Med. Sci. 7, 259 (1971).PubMedGoogle Scholar
  23. 23.
    Singer, J.D., Cotlier, E., and Krimmer, R., Hexosaminidase A in tears and saliva for rapid identification of Tay-Sachs disease and its carriers. Lancet 2, 1116 (1973).CrossRefGoogle Scholar
  24. 24.
    Perle, G., and Saifer, A., Methods for pre-and postnatal detection of Tay-Sachs disease heterozygotes (carriers) and homozygotes (patients) by means of hexosaminidase analysis of their fluids and tissues. In “Amniotic Fluid”. S. Natelson, A. Scommegna and M.B. Epstein, Eds. J. Wiley & Sons, New York, N.Y., 1974, pp 373–381.Google Scholar
  25. 25.
    Sandman, R., Margules, R.M., and Kountz, S.L., Urinary liposomal glycosidases after renal allotransplantation: correlation of enzyme excretion with allograft rejection and ischemia. Clin. Chim. Acta 45, 349 (1973).CrossRefGoogle Scholar
  26. 26.
    Hultberg, B., Ockerman, P.A., Norden, N.E., Isoenzymes of four acid hydrolases in human kidney and urine. Clin. Chim. Acta 52, 239 (1974).CrossRefGoogle Scholar
  27. 27.
    Grebner, E.E., and Tucker, J., Human urinary N-acetyl-β-hexosaminidases. Biochim. Biophys. Acta 321, 228 (1973).Google Scholar
  28. 28.
    Goldberg, M.F., The use of tears for heterozygote detection and genetic counseling (An editorial). Invest. Ophthal. 13, 159 (1974).PubMedGoogle Scholar
  29. 29.
    Johnson, D.L., Del Monte, M.A., Cotlier, E., and Desnick, R.J., Fabry disease: Diagnosis by α-galactosidase activities in tears. Clin.Chim.Acta 63, 81(1975).CrossRefGoogle Scholar
  30. 30.
    O’Brien, J.S., Ho, M.W., Okada, S., Zielke, K., Veath, M.L., and Tennant, L., Sphingolipidoses: Detection of heterozygotes and homozygotes. In “Sphingolipids, Sphingolipidoses and Allied Disorders”. B.W. Volk and S.M. Aronson, Eds. Plenum Press, New York, N.Y., 1972, pp 581–597.Google Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Abraham Saifer
    • 1
  • June Amoroso
    • 1
  • Guta Perle
    • 1
  1. 1.Department of BiochemistryIsaac Albert Research Institute of the Kingsbrook Jewish Medical CenterBrooklynUSA

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