CARRIER FREQUENCIES FOR SANDHOFF DISEASE (SHD) AND TAY-SACHS (TSD) IN AMERICAN JEWISH (J) AND NON-JEWISH (NJ) POPULATIONS

Abstract

Serum hexosaminidase (HEX) profiles from 59,805 J and 42,477 NJ individuals screened for TSD heterozygote status were used to estimate the SHD and TSD carrier frequencies in these populations. Mean levels of total HEX (T-HEX) and % heat labile HEX (% HEX-A) in sera differ among noncarriers (NC), obligate TSD carriers (TSD C) and obligate SHD carriers (SHD C) as follows: A 95% bivariate isodensity ellipse has been constructed with T-HEX and % HEX-A values from 31 obligate SHD heterozygotes. The ellipse identifies suspect SHD C with 95% sensitivity and a 1-3% false positive rate. Cluster analysis and a derived linear discriminant function from retest serum and leukocyte T-HEX and % HEX-A values discriminates between true SHD C and NC. The TSD C frequency is 1/801 in J and 1/414 in NJ. These estimates are consistent with SHD incidence data from our national surveillance program. The TSD C frequency in J is 1/28, while a TSD C rate in NJ of 1/90 has been observed. The NJ TSD C rate is not consistent with disease incidence data. Rather, it is probable that 70% of the NJ identified as TSD C may be heterozygotes for other partial HEX-A mutations, and therefore at risk for other GM2 ganglioside storage disorders.