Automated determination of serum hexosaminidase A by pH inactivation for detection of Tay-Sachs disease heterozygotes.

We have automated a manual test for detection of heterozygotes of Tay-Sachs disease by assay of hexosaminidase A in serum, based on pH inactivation [C/in. Chim. Acta 43, 417 (1973)]. The same manifold is used both for the total hexosaminidase and pH-inactivation (hexosaminidase B) procedures. Automation expedites mass screening of the Ashkenazi Jewish population for carriers of the TaySachs gene (prevalence rate, 1:30), because 100 or more tests can be performed daily. The mean percentage value and range (±2 SD) of hexosaminidase A for normal adults is 68.6 (58-79) and for carriers is 48.8 (39-59) with the automated pH-inactivation procedure. “Presumed carriers” (<53% hexosaminidase A) and individuals in the uncertain range (53 to 58%) should be retested by using leukocytes, to avoid the effect of certain physical ailments, before being labeled as carriers. The same automated system used for this assay can also be used to detect carriers of at least seven other sphingolipidoses for which artificial fuorogenic substrates are available.