Specificity and sensitivity of hexosaminidase assays and DNA analysis for the detection of Tay-Sachs disease gene carriers among Ashkenazic Jews.

Tay-Sachs disease (TSD), a neurodegenerative disorder resulting from a deficiency of the lysosomal enzyme hexosaminidase A (HexA), clusters in Ashkenazic Jews. Population-based screening programs to detect carriers of TSD genes by means of HexA assays have been active since the 1970s. The recent characterization of 3 mutations in the HEXA gene (in exon 7, exon 11, and intron 12), which account for over 90% of HEXA mutations in Ashkenazim, appeared to offer better options for screening and diagnosis. The relative frequencies of the three mutations in Montreal are similar to those reported in four other North American populations. We compared enzyme and DNA analyses to determine specificity and sensitivity of each test when the other was used as the confirmatory procedure. Neither procedure has a sensitivity of 1.0. Maximum sensitivity and specificity were achieved by using both tests together. The findings here are likely to apply to most cases where the variant screened enzyme phenotype can result from more than one mutation.