A new variant of Sandhoff's disease.

Abstract

Extract: A 28-month-old Negro male with atypical Sandhoff's disease (GM2 gangliosidosis, type 2) is described. Clinical presentation closely resembled Sandhoff's disease. The appendiceal neuron cytoplasm was distended with periodic acid-Schiff (PAS)-positive material. Hepatic glycolipid N-acetylneuraminic acid was elevated 1.5-fold, chiefly because of increased GM2. Neutral glycolipid hexose was elevated twofold, mainly because of a component with globoside-like chromatographic properties. Unlike patients with Sandhoff's disease, the child had total β-D-N-acetylhexosaminidase activity 20–24% of normal in serum and plasma and 7–11% of normal in leukocytes and cultured fibroblasts, but activity in liver (<2% of normal) was similar to that in Sandhoff's disease. In all tissues examined, >95% of the activity was heat denaturable, corresponding in electrophoretic mobility to the heat-denaturable component of normal tissues. The decrease in heat-denaturable activity with time and the pH optimum were similar in patient and control crude tissue preparations and partially purified preparations of plasma hexosaminidase A. In the child's mother, total hexosaminidase activity was approximately 50% of mean control values in serum, plasma, and leukocytes, and serum hexosaminidase A was relatively increased. This finding, together with the death of at least three other children in the kindred from an apparently phenotypically similar illness, indicates the inherited nature of the disorder.Speculation: Appreciable hexosaminidase activity in serum and plasma and its marked deficiency in liver suggest that the active form (or forms) in serum and plasma differ from those in solid tissues, and that the mutation in the case described has altered the hexosaminidases in a manner that virtually abolishes their activity in solid tissues but permits their partial activity in serum and plasma.