Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations.

Carrier frequencies for the allele(s) causing Sandhoff disease have been estimated for the U.S. Jewish and non-Jewish populations. The estimates have been made directly, with data from 22,043 Jewish and 32,342 non-Jewish individuals measured for total serum hexosaminidase activity and the heat-labile fraction. These values have been shown to identify potential carriers of the Sandhoff allele(s) with 95% sensitivity. Subsequent leukocyte assays of total hexosaminidase activity and the heat-labile fraction in those identified in serum tests have been shown to provide a much finer discrimination between those who carry the allele(s) and those who do not. Results from such assays were used to generate these carrier frequency estimates. Carrier frequency estimates have also been made indirectly from Sandhoff disease incidence data collected during the period 1979-84. These estimates are in agreement with data for the Jewish population under analysis, but in the non-Jewish population the estimate derived from data on screened individuals is greater than the estimate derived from incidence figures. The possible causes for such a difference are discussed. In a study of non-Jewish individuals each of whose grandparents derives from a single country of origin, the distribution of countries among Sandhoff disease carriers differs significantly from that in the non-Jewish sample under analysis, indicating possible ethnic groups with increased or decreased carrier frequencies. These analyses suggest an increased Sandhoff disease carrier frequency among Mexican and Central-American populations and a decreased carrier frequency among non-Jewish German populations.