Tay-Sachs Disease

doi:10.1017/CHOL9780521332866.199

VIII.137 - Tay-Sachs Disease

from Part VIII - Major Human Diseases Past and Present

Published online by Cambridge University Press: 28 March 2008

Bradford Towne

Edited by

Kenneth F. Kiple

Show author details

Kenneth F. Kiple: Affiliation:
Bowling Green State University, Ohio

Book contents

Get access

Summary

Tay-Sachs disease (TSD) is the best known of the sphingolipidoses, a group of genetic disorders that includes Niemann-Pick disease, Gaucher’s disease, and others. Specifically, TSD is GM2 (beta) gangliosidosis, an autosomal recessive disease with complete penetrance. Affected individuals (recessive homozygotes) produce virtually no functional hexosaminidase A (hex A), an enzyme necessary for normal neurological development and function. TSD is very rare in most populations, but is, overall, about 100 times more prevalent among Ashkenazi Jews. This indicates that the TSD gene frequency is about 10 times higher in the Ashkenazi Jewish population. Persons with the disease usually show clinical symptoms of neurological degeneration by 6 months of age. Their condition steadily deteriorates, and they seldom live beyond the age of 4 years. There is no cure, but heterozygous “carriers” of the defective gene can be identified by clinical test, and amniocentesis can detect an affected fetus.

History

The British ophthalmologist Warren Tay (1881) first reported some of the early clinical signs of TSD. In the United States, Bernard Sachs (1887) further documented the clinical course and pathology of the disease he later called “amaurotic family idiocy” (Sachs 1896). 1896). It was Sachs who first noted the familial nature of the disease, and its seemingly exclusive occurrence in Jewish families. However, reports were soon made of non-Jewish cases. D. Slome (1933) was the first to survey the literature on the population characteristics of TSD and confirmed the disease’s autosomal recessive mode of transmission as well as the TSD gene’s higher frequency among Jews.

Type: Chapter
Information: The Cambridge World History of Human Disease , pp. 1036 - 1043

DOI: https://doi.org/10.1017/CHOL9780521332866.199 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 1993

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Adachi, M., and Volk, B. W.. 1975. Pathology. In The gangliosidoses, ed. Volk, B. W. and Schneck, L.. New York.Google Scholar

Aronson, S. M. 1964. Epidemiology. In Tay–Sachs disease, ed. Volk, B. W.. New York.Google Scholar

Bach, G., et al. 1976. Tay–Sachs disease in a Moroccan Jewish family: A possible new mutation. Israeli Journal of Medical Science 12.Google Scholar

Chakravarti, A., and Chakraborty, R.. 1978. Elevated frequency of Tay–Sachs disease among Ashkenazic Jews unlikely by genetic drift alone. American Journal of Human Genetics 30.Google Scholar PubMed

Chase, G. A., and McKusick, V. A.. 1972. Controversy in human genetics: Founder effect in Tay–Sachs disease. American Journal of Human Genetics 24.Google Scholar PubMed

Chern, C. J., et al. 1977. Assignment of the structural genes for the α subunit of hexosaminidase A, mannose phosphate isomerase, and pyruvate kinase to the region q22–qter of human chromosome 15. Somatology of Cell Genetics 3.Google Scholar PubMed

Fraikor, A. L. 1977. Tay–Sachs disease: Genetic drift among the Ashkenazic Jews. Social Biology 24.CrossRef Google Scholar

Gilbert, F., et al. 1975. Tay–Sachs’ and Sandhoff’s diseases: The assignment of genes for hexosaminidase A and B to individual human chromosomes. Proceedings of the National Academy of Sciences of the United States of America 72.CrossRef Google Scholar

Greenberg, D. A., and Kaback, M. M.. 1982. Estimation of the frequency of hexosaminidase A variant alleles in the American Jewish population. American Journal of Human Genetics 34.Google Scholar PubMed

Kaback, M. M. 1979. Tay–Sachs disease: Screening and prevention. New York.Google Scholar

Kaback, M. M. 1981. Heterozygote screening and prenatal diagnosis in Tay–Sachs disease: A worldwide update. In Lysozymes and lysosomal storage diseases, ed. Callahan, J. W. and Lowden, J. A.. New York.Google Scholar

Kaback, M. M., and Zeiger, R. S.. 1972. Heterozygote detection in Tay–Sachs disease: A prototype community screening program for the prevention of recessive genetic disorders. In Sphingolipids, sphingolipidoses, and allied disorders, ed. Volk, B. W. and Aronson, S. M.. New York.Google Scholar

Kelly, T. E., et al. 1975. Tay–Sachs disease: High gene frequency in a non–Jewish population. American Journal of Human Genetics 27.Google Scholar

Kidd, K. K., Klinger, H. P., and Ruddle, F. H., eds. 1989 Human gene mapping, Vol. 10. Basel.Google Scholar

Klenk, E. 1942. Ueber die Ganglioside des Gehirns bei der infantilen amaurotischen idiotie vom Typus Tay–Sachs. Berichte der Deutschen Chemischen Gesellschaft 75.Google Scholar

Knudson, A. G., and Kaplan, W. D.. 1962. Genetics of the sphingolipidoses. In Cerebral sphingolipidoses: A symposium on Tay–Sachs disease and allied disorders, eds. Aronson, S. M. and Volk, B. W.. New York.Google Scholar

Koestler, A. 1976. The thirteenth tribe. New York.Google Scholar

Kolodny, E. H. 1979. Tay–Sachs disease. In Genetic diseases among Ashkenazi Jews, ed. Goodman, R. M. and Motulsky, A. G.. New York.Google Scholar

Lalley, P. A., et al. 1974. Human β-D-ε-Acety lhexosaminidases A and B: Expression and linkage relationship in somatic cell hybrids. Proceedings of the National Academy of Sciences of the United States of America 71.CrossRef Google Scholar

Myerowitz, R., and Hogikyan, N. D.. 1986. Different mutations in Ashkenazi Jewish and non-Jewish French Canadians with Tay–Sachs disease. Science 232.CrossRef Google Scholar PubMed

Myerowitz, R., et al. 1985. Human β-hexosaminidase α chain: Coding sequence and homology with the chain. Proceedings of the National Academy of the United States of America 82.CrossRef Google Scholar PubMed

Myrianthopoulos, N. C. 1962. Some epidemiologic and genetic aspects of Tay–Sachs disease. In Cerebral sphingolipidoses: A symposium on Tay–Sachs disease and allied disorders, ed. Aronson, S. M. and Volk, B. W.. New York.Google Scholar

Myrianthopoulos, N. C., and Aronson, S. M.. 1966. Population dynamics of Tay–Sachs disease. I. Reproductive fitness and selection. American Journal of Human Genetics 18.Google Scholar

Myrianthopoulos, N. C., and Aronson, S. M.. 1967. Reproductive fitness and selection in Tay–Sachs disease. In Inborn disorders of sphingolipid metabolism, ed. Aronson, S. M. and Volk, B. W.. New York.Google Scholar

Myrianthopoulos, N. C., and Aronson, S. M.. 1972. Population dynamics of Tay–Sachs disease. II. What confers the selective advantage upon the Jewish heterozygote? In Sphingolipids, sphingolipidoses, and allied disorders, ed. Volk, B. W. and Aronson, S. M.. New York.Google Scholar

Myrianthopoulos, N. C., Naylor, A. F., and Aronson, S. M.. 1970. Tay–Sachs disease is probably not increasing. Nature 227.CrossRef Google Scholar

Nakai, H., Ryers, M. G., and Shows, T. B.. 1987. Mapping HEX A to 15q23–q24. Cytogenetics and Cell Genetics 46: [A1188].Google Scholar

Navon, R., and Padeh, B.. 1971. Prenatal diagnosis of Tay–Sachs genotypes. British Medical Journal 4.CrossRef Google Scholar PubMed

Neel, J. V. 1979. History and the Tay–Sachs allele. In Genetic diseases among Ashkenazi Jews, ed. Goodman, R. M. and Motulsky, A. G.. New York.Google Scholar

O’Brien, J. S. 1983. The gangliosides. In The metabolic basis of inherited disease, ed. Stanbury, J. B. et al.. New York.Google Scholar

O’Brien, J. S., et al. 1970. Tay–Sachs disease: Detection of heterozygotes and homozygotes by serum hexosaminidase assay. New England Journal of Medicine 283.Google Scholar PubMed

O’Brien, J. S., 1971. Tay–Sachs disease: Prenatal diagnosis. Science 172.Google Scholar PubMed

Okada, S., and O’Brien, J. S.. 1969. Tay–Sachs disease: Generalized absence of β-D-ε-acetylhexosaminidase component. Science 165.CrossRef Google Scholar PubMed

Rao, D. C., and Morton, N. E.. 1973. Large deviations in the distribution of rare genes. American Journal of Human Genetics 25.Google Scholar PubMed

Rapport, M. M. 1981. Introduction to the biochemistry of gangliosides. In Gangliosides in neurological and neuromuscular function, development, and repair, ed. Rapport, M. M. and Gorio, A.. New York.Google Scholar

Robinson, D., and Stirling, J. L.. 1968. ε-Acetyl-β-glucosaminidases in human spleen. Biochemical Journal 107.CrossRef Google Scholar PubMed

Sachs, B. 1887. On arrested cerebral development with special reference to its cortical pathology. Journal of Nervous and Mental Disease 14.CrossRef Google Scholar

Sachs, B. 1896. A family form of idiocy, generally fatal, associated with early blindness. Journal of Nervous and Mental Disease 23.Google Scholar

Schneck, L., et al. 1970. Prenatal diagnosis of Tay–Sachs disease. Lancet 1.Google Scholar PubMed

Shaw, R. F., and Smith, A. P.. 1969. Is Tay–Sachs disease increasing?Nature 224.CrossRef Google Scholar PubMed

Slome, D. 1933. The genetic basis of amaurotic family idiocy. Journal of Genetics 27.CrossRef Google Scholar

Svennerholm, L. 1962. The chemical structure of normal human brain and Tay–Sachs gangliosides. Biochemical and Biophysical Research Communications 9.CrossRef Google Scholar PubMed

Svennerholm, L. 1980. Gangliosides and synaptic transmission. In Structure and function of gangliosides, ed. Svennerholm, L. et al.. New York.CrossRef Google Scholar

Tanaka, A., et al. 1990. GM2-gangliosidosis B1 variant: Analsyis of β-hexosaminidase α gene abnormalities in seven patients. American Journal of Human Genetics 46.Google Scholar

Tay, W. 1881. Symmetrical changes in the region of the yellow spot in each eye of an infant. Ophthalmological Society of the United Kingdom 1.Google Scholar

Triggs-Raine, B. L., et al. 1989. Ashkenazi Tay–Sachs disease: A comparison of DNA- and enzyme-based methods for carrier testing. American Journal of Human Genetics (supplement) 45.Google Scholar

Volk, B. W., Schneck, L., and Adachi, M.. 1970. Clinic, pathology and biochemistry of Tay–Sachs disease. In Handbook of clinical neurology, Vol. 10: Leucodystrophies and poliodystrophies, ed. Vinken, P. J. and Bruyn, G. W.. Amsterdam.Google Scholar

Wagener, D., and Cavalli-Sforza, L. L.. 1975. Ethnic variation in genetic disease: Possible roles of hitchhiking and epistasis. American Journal of Human Genetics 27.Google Scholar PubMed

Wagener, D., Cavalli-Sforza, L. L., and Barakat, R.. 1978. Ethnic variation of genetic disease: Roles of drift for recessive lethal genes. American Journal of Human Genetics 30.Google Scholar PubMed

Wilson, E. O., and Bossert, W. H.. 1971. A primer of population biology. Sunderland, Mass.Google Scholar

Wright, S. 1977. Evolution and the genetics of populations, Vol. 3: Experimental results and evolutionary deductions. Chicago.Google Scholar

Zlotogora, J., et al. 1980. Metachromatic leukodystrophy in the Habbanite Jews: High frequency in a genetic isolate and screening for heterozygotes. American Journal of Human Genetics 32.Google Scholar

Zlotogora, J., Zeigler, M., and Bach, G.. 1988. Selection in favor of lysosomal storage disorders?American Journal of Human Genetics 42.Google Scholar PubMed