Diagnosis of Tay-Sachs disease using [H]N-acetylneuraminic acid labelled GM2 ganglioside as substrate

G_M2 ganglioside labelled with tritium in the N-acetylneuraminic acid moiety was prepared and used to measure β-hexosaminidase A activity in cultured human skin fibroblast extracts. The latter convert this substrate to the correspondingly labelled G_M3 ganglioside which can easily be separated from the substrate by thin-layer chromatography. No cleavage of the N-acetylneuraminic acid group was observed under our conditions.Two methods are described for the determination of G_M2-β-hexosaminidase A activity in fibroblasts. The application of these methods to the diagnosis of Tay-Sachs disease is discussed.