Tay-Sachs disease (TSD) is an autosomal recessive, progressive, and fatal neurodegenerative disorder. Within the last 25 years, the discovery of the enzymatic basis of the disease, the deficiency of the enzyme hexosaminidase A, has made possible both enzymatic diagnosis of TSD and heterozygote identification. TSD is the first genetic condition for which a community-based heterozygote screening program was attempted with the intention of reducing the incidence of a genetic disease. In this article we review the clinical, biochemical, and molecular features of TSD as well as the development of laboratory technology that has been deployed in community genetic screening programs. We describe the assay procedures used and some of the limitations in their accuracy. We consider the impact of DNA-based technology on the process of identification of individuals carrying mutant genes associated with TSD and we discuss the social context within which genetic screening occurs.
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