Tay-Sachs disease (TSD) is a neurodegenerative disorder resulting from deficiency of the lysosomal enzyme hexosaminidase A (HEX A), resulting in accumulation of the cell membrane glycolipid GM2 ganglioside within lyso-somes (for review, see References 10 and 11). The clinical course of TSD is characterized by normal development for the first few months of life followed by progressive loss of motor skills, macrocephaly, seizures, blindness, and death usually before 4 years of age. Infantile TSD is always fatal, and there is no effective treatment. There are also later-onset forms with slower disease progression. TSD is an autosomal recessive disease and has a carrier frequency of approximately 1 in 30 Ashkenazi Jewish individuals and 1 in 250 to 300 in most other populations. Genetic isolates such as the French Canadians of Quebec, Cajuns from Louisiana, and the Amish in Pennsylvania also have carrier frequencies similar to that seen in Ashkenazi Jews. The first carrier screening programs began in 1970 and used the measurement of HEX A activity in serum, leukocytes, or tears. When the HEXA gene encoding HEX A was cloned in 1987, disease-associated mutations were identified. Current testing for TSD utilizes both biochemical and molecular testing by various methods.
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