Diagnosis of Tay-Sachs disease by estimation of beta-N-acetylhexosaminidase activity using a radiolabeled hyaluronic acid-derived trisaccharide substrate.

We have prepared a new radiolabeled substrate (N-[3H]acetylglucosamine-glucuronic acid-N-[3H]acetylglucosamine), from hyaluronic acid, for an assay of beta-N-acetylhexosaminidase activity. Using this substrate, we found a striking deficiency of beta-N-acetylhexosaminidase activity in cultured skin fibroblasts and in liver homogenates from patients with Tay-Sachs disease. DEAE-cellulose chromatography at pH 6.0 revealed that both isoenzymes A and B of beta-N-acetylhexosaminidase from normal liver participated in the catabolism of hyaluronic acid. There were, however, major differences in substrate specificities between isoenzymes A and B. Our results indicate that this substrate should be useful for enzymatic diagnosis of Tay-Sachs disease.