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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1986 Apr;38(4):505–514.

Two abnormalities of hexosaminidase A in clinically normal individuals.

E E Grebner, D A Mansfield, S S Raghavan, E H Kolodny, A d'Azzo, E F Neufeld, L G Jackson
PMCID: PMC1684809  PMID: 2939713

Abstract

Two abnormalities of beta-hexosaminidase A (HEX A) activity are described. One, found in two unrelated Jewish children, was characterized by the complete absence of HEX A activity in serum, but low levels of activity in leukocytes and fibroblasts using artificial substrate. The other, found in a non-Jewish man, was characterized by uniformly low levels of HEX A activity in leukocytes, fibroblasts, and serum against artificial substrate. In all cases, the pH optimum of HEX A was normal, there was no increased lability at 37 degrees C, and no inhibitor was detected to account for the deficiency of activity. Cultured fibroblasts of these individuals were capable of synthesizing and processing alpha- and beta-subunits of HEX A and capable of cleaving GM2 ganglioside. The patients, ranging in age from 6 to 30 years, are clinically normal. They are probably genetic compounds carrying the classical Tay-Sachs gene and a differently mutated allele that imparts the anomalous phenotypic features observed.

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Selected References

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

  1. Conzelmann E., Sandhoff K. Partial enzyme deficiencies: residual activities and the development of neurological disorders. Dev Neurosci. 1983;6(1):58–71. doi: 10.1159/000112332. [DOI] [PubMed] [Google Scholar]
  2. Grebner E. E., Jackson L. G. Prenatal diagnosis of Tay-Sachs disease: studies on the reliability of hexosaminidase levels in amniotic fluid. Am J Obstet Gynecol. 1979 Jul 1;134(5):547–550. doi: 10.1016/0002-9378(79)90838-x. [DOI] [PubMed] [Google Scholar]
  3. Greenberg D. A., Kaback M. M. Estimation of the frequency of hexosaminidase a variant alleles in the American Jewish population. Am J Hum Genet. 1982 May;34(3):444–451. [PMC free article] [PubMed] [Google Scholar]
  4. Hasilik A., Neufeld E. F. Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J Biol Chem. 1980 May 25;255(10):4937–4945. [PubMed] [Google Scholar]
  5. Kaback M. M., Shapiro L. J., Hirsch P., Roy C. Tay-Sachs disease heterozygote detection: a quality control study. Prog Clin Biol Res. 1977;18:267–279. [PubMed] [Google Scholar]
  6. Kelly T. E., Reynolds L. W., O'Brien J. S. Segregation within a family of two mutant alleles for hexosaminidase A. Clin Genet. 1976 May;9(5):540–543. doi: 10.1111/j.1399-0004.1976.tb01609.x. [DOI] [PubMed] [Google Scholar]
  7. Navon R., Geiger B., Yoseph Y. B., Rattazzi M. C. Low levels of beta hexosaminidase A in healthy individuals with apparent deficiency of this enzyme. Am J Hum Genet. 1976 Jul;28(4):339–349. [PMC free article] [PubMed] [Google Scholar]
  8. O'Brien J. S., Tennant L., Veath M. L., Scott C. R., Bucknall W. E. Characterization of unusual hexosaminidase A (HEX A) deficient human mutants. Am J Hum Genet. 1978 Nov;30(6):602–608. [PMC free article] [PubMed] [Google Scholar]
  9. Proia R. L., d'Azzo A., Neufeld E. F. Association of alpha- and beta-subunits during the biosynthesis of beta-hexosaminidase in cultured human fibroblasts. J Biol Chem. 1984 Mar 10;259(5):3350–3354. [PubMed] [Google Scholar]
  10. Raghavan S., Krusell A., Lyerla T. A., Bremer E. G., Kolodny E. H. GM2-ganglioside metabolism in cultured human skin fibroblasts: unambiguous diagnosis of GM2-gangliosidosis. Biochim Biophys Acta. 1985 Apr 25;834(2):238–248. doi: 10.1016/0005-2760(85)90161-4. [DOI] [PubMed] [Google Scholar]
  11. Sandhoff K., Christomanou H. Biochemistry and genetics of gangliosidoses. Hum Genet. 1979;50(2):107–143. doi: 10.1007/BF00390234. [DOI] [PubMed] [Google Scholar]
  12. Thomas G. H., Raghavan S., Kolodny E. H., Frisch A., Neufeld E. F., O'Brien J. S., Reynolds L. W., Miller C. S., Shapiro J., Kazazian H. H., Jr Nonuniform deficiency of hexosaminidase A in tissues and fluids of two unrelated individuals. Pediatr Res. 1982 Mar;16(3):232–237. doi: 10.1203/00006450-198203000-00014. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. d'Azzo A., Proia R. L., Kolodny E. H., Kaback M. M., Neufeld E. F. Faulty association of alpha- and beta-subunits in some forms of beta-hexosaminidase A deficiency. J Biol Chem. 1984 Sep 10;259(17):11070–11074. [PubMed] [Google Scholar]

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