Nonuniform deficiency of hexosaminidase a in tissues and fluids of two unrelated individuals

George H. Thomas, Srinivasa Raghavan, Edwin H. Kolodny, Amos Frisch, Elizabeth F. Neufeld, John S. O’Brien, Linda W. Reynolds, Carol S. Miller, Julie Shapiro, Haig H. Kazazian, Richard H. Heller

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Serum samples from two unrelated, clinically normal individuals lacked detectable hexosaminidase A by heat inactivation and electrophoretic analysis. In contrast, 15 and 17% of the hexosaminidase in their leukocytes and 23 and 26% of the hexosaminidase of their cultured fibroblasts had the heat stability and electrophoretic properties of the A form of this enzyme. An in vitro measurement of fibroblasts GM2 ganglioside-β-galactosaminidase was in the range expected for Tay-Sachs disease (TSD) heterozygotes (2.5 and 3.1 versus a normal mean of 3.7). In contrast, fibroblasts from a patient with TSD, analyzed in an identical fashion, contained no detectable activity. Ten days after addition of labeled GM2 ganglioside to the medium of the cultured fibroblasts, 43 and 59% of the radioactivity taken up by the cells of these patients remained as unhydrolyzed ganglioside as compared with 94% in TSD fibroblasts and 42% in control cells. An analysis of sphingolipid composition by high performance liquid chromatography although the endogenous level of GM2 was elevated in TSD fibroblasts (0.39 nmoles/mg protein) there was no increase in the cells of these patients (0 and 0.12 versus control of 0.17 nmoles/mg protein). Finally, the synthesis of hexosaminidase was examined by an electrophoretic analysis of immunoprecipitates of the enzyme precursors that had been radiolabeled by culturing fibroblasts in medium containing [3H]-leucine. These studies revealed a normal pattern of biosynthesis, processing and secretion of the α and β chains. The ratio of the α chain to the β chain, however, was in the range expected for TSD heterozygotes. Speculation: In all likelihood, these individuals suffer from a genetic or physiologic abnormality that results in the absence of hexosaminidase A in serum and a relative preservation of activity against both GM2 ganglioside and 4-methylumbelliferyl-N-acetyl-y3-glu- cosaminide in cultured fibroblasts.

Original languageEnglish (US)
Pages (from-to)232-237
Number of pages6
JournalPediatric research
Issue number3
StatePublished - Mar 1982

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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