Sandhoff disease: impaired catabolism of sulfated glycosaminoglycans in cultured fibroblasts.

Fibroblasts cultured from the skin of patients with Sandhoff disease accumulate excessive amounts of sulfated glycosaminoglycans because of degradative inadequacy. Only a slight such abnormality in the metabolism of sulfated glycosaminoglycans was seen in fibroblasts from patients with Tay-Sachs disease. The defective glycosaminoglycan catabolism in Sandhoff fibroblasts is specifically corrected by intracellular replacement of beta-N-acetyl-hexosaminidase. Both beta-N-acetyl-hexosaminidase A and B are effective in bringing about such correction, although there seem to be differences in specificity. Our findings suggest that in Sandhoff disease there is an impaired catabolism of glycosaminoglycans in addition to the defect in the degradation of glycosphingolipids.