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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1976 Jul;28(4):339–349.

Low levels of beta hexosaminidase A in healthy individuals with apparent deficiency of this enzyme.

R Navon, B Geiger, Y B Yoseph, M C Rattazzi
PMCID: PMC1685065  PMID: 941901

Abstract

Appreciable beta hexosaminidase A (hex A) activity has been detected in cultured skin fibroblasts and melanoma tissue from healthy individuals previously reported as having deficiency of hex A activity indistinguishable from that of patients with Tay-Sachs disease (TSD). Identification and quantitation of hex A, amounting to 3.5%-6.9% of total beta hexosaminidase activity, has been obtained by cellulose acetate gel electrophoresis, DEAE-cellulose ion-exchange chromatography, radial immunodiffusion, and radioimmunoassay. Previous family studies suggested that these individuals may be compound heterozygotes for the common mutant TSD gene and a rare (allelic) mutant gene. Thus, the postulated rate mutant gene appears to code for the expression of low amounts of hex A. Heterozygotes for the rare mutant may be indistinguishable from heterozygotes for the common TSD mutant. However, direct visualization and quantitation of hex A by the methods described may prevent false-positive prenatal diagnosis of TSD in fetuses having the incomplete hex A deficiency of the type described in the four healthy individuals.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bach G., Suzuki K. Heterogeneity of human hepatic H-acetyl-beta-D-hexosaminidose. A activity toward natural glycosphingolipid substrates. J Biol Chem. 1975 Feb 25;250(4):1328–1332. [PubMed] [Google Scholar]
  2. Bartholomew W. R., Rattazzi M. C. Immunochemical characterization of human beta-D-N-acetyl hexosaminidase from normal individuals and patients with Tay-Sachs disease. I. Antigenic differences between hexosaminidase A and hexosaminidase B. Int Arch Allergy Appl Immunol. 1974;46(4):512–524. doi: 10.1159/000231154. [DOI] [PubMed] [Google Scholar]
  3. Ben-Yoseph Y., Geiger B., Arnon R. Antibody-mediated thermal stabilization of human hexosaminidases. Immunochemistry. 1975 Mar;12(3):221–226. doi: 10.1016/0019-2791(75)90235-9. [DOI] [PubMed] [Google Scholar]
  4. Cantz M., Kresse H. Sandhoff disease: defective glycosaminoglycan catabolism in cultured fibroblasts and its correction by beta-N-acetylhexosaminidase. Eur J Biochem. 1974 Sep 16;47(3):581–590. doi: 10.1111/j.1432-1033.1974.tb03729.x. [DOI] [PubMed] [Google Scholar]
  5. Dreyfus J. C., Poenaru L., Svennerholm L. Absence of hexosaminidase A and B in a normal adult. N Engl J Med. 1975 Jan 9;292(2):61–63. doi: 10.1056/NEJM197501092920201. [DOI] [PubMed] [Google Scholar]
  6. Geiger B., Ben-Yoseph Y., Arnon R. Purification of human hexosaminidases A and B by affinity chromatography. FEBS Lett. 1974 Sep 1;45(1):276–281. doi: 10.1016/0014-5793(74)80861-6. [DOI] [PubMed] [Google Scholar]
  7. Kolodny E. H., Brady R. O., Volk B. W. Demonstration of an alteration of ganglioside metabolism in Tay-Sachs disease. Biochem Biophys Res Commun. 1969 Oct 22;37(3):526–531. doi: 10.1016/0006-291x(69)90947-4. [DOI] [PubMed] [Google Scholar]
  8. Li Y. T., Mazzotta M. Y., Wan C. C., Orth R., Li S. C. Hydrolysis of Tay-Sachs ganglioside by beta-hexosaminidase A of human liver and urine. J Biol Chem. 1973 Nov 10;248(21):7512–7515. [PubMed] [Google Scholar]
  9. Marchalonis J. J. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem J. 1969 Jun;113(2):299–305. doi: 10.1042/bj1130299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nadler H. L. Patterns of enzyme development utilizing cultivated human fetal cells derived from amniotic fluid. Biochem Genet. 1968 Sep;2(2):119–126. doi: 10.1007/BF01458711. [DOI] [PubMed] [Google Scholar]
  11. Navon R., Padeh B., Adam A. Apparent deficiency of hexosaminidase A in healthy members of a family with Tay-Sachs disease. Am J Hum Genet. 1973 May;25(3):287–293. [PMC free article] [PubMed] [Google Scholar]
  12. O'Brien J. S., Okada S., Chen A., Fillerup D. L. Tay-sachs disease. Detection of heterozygotes and homozygotes by serum hexosaminidase assay. N Engl J Med. 1970 Jul 2;283(1):15–20. doi: 10.1056/NEJM197007022830104. [DOI] [PubMed] [Google Scholar]
  13. Okada S., O'Brien J. S. Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science. 1969 Aug 15;165(3894):698–700. doi: 10.1126/science.165.3894.698. [DOI] [PubMed] [Google Scholar]
  14. Padeh B., Navon R. Diagnosis of Tay-Sachs disease by hexosaminidase activity in leukocytes and amniotic fluid cells. Isr J Med Sci. 1971 Feb;7(2):259–263. [PubMed] [Google Scholar]
  15. Rattazzi M. C., Brown J. A., Davidson R. G., Shows T. B. Studies on complementation of beta hexosaminidase deficiency in human GM2 gangliosidosis. Am J Hum Genet. 1976 Mar;28(2):143–154. [PMC free article] [PubMed] [Google Scholar]
  16. Robinson D., Stirling J. L. N-Acetyl-beta-glucosaminidases in human spleen. Biochem J. 1968 Apr;107(3):321–327. doi: 10.1042/bj1070321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sandhoff K., Harzer K., Wässle W., Jatzkewitz H. Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. J Neurochem. 1971 Dec;18(12):2469–2489. doi: 10.1111/j.1471-4159.1971.tb00204.x. [DOI] [PubMed] [Google Scholar]
  18. Sandhoff K., Wässle W. Anreicherung und Charakterisierung zweier Formen der menschlichen N-acetyl- -D-hexosaminidase. Hoppe Seylers Z Physiol Chem. 1971 Aug;352(8):1119–1133. [PubMed] [Google Scholar]
  19. Srivastava S. K., Beutler E. Studies on human beta-D-N-acetylhexosaminidases. 3. Biochemical genetics of Tay-Sachs and Sandhoff's diseases. J Biol Chem. 1974 Apr 10;249(7):2054–2057. [PubMed] [Google Scholar]
  20. Tallman J. F., Brady R. O., Navon R., Padeh B. Ganglioside catabolism in hexosaminidase A-deficient adults. Nature. 1974 Nov 15;252(5480):254–255. doi: 10.1038/252254a0. [DOI] [PubMed] [Google Scholar]
  21. Tallman J. F., Brady R. O., Quirk J. M., Villalba M., Gal A. E. Isolation and relationship of human hexosaminidases. J Biol Chem. 1974 Jun 10;249(11):3489–3499. [PubMed] [Google Scholar]
  22. Vidgoff J., Buist N. R., O'Brien J. S. Absence of -N-acetyl-D-hexosaminidase A activity in a healthy woman. Am J Hum Genet. 1973 Jul;25(4):372–381. [PMC free article] [PubMed] [Google Scholar]
  23. Wenger D. A., Okada S., O'Brien J. S. Studies on the substrate specificity of hexosaminidase A and B from liver. Arch Biochem Biophys. 1972 Nov;153(1):116–129. doi: 10.1016/0003-9861(72)90427-4. [DOI] [PubMed] [Google Scholar]

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