Accumulation of Lysosphingolipids in Tissues from Patients with GM1 and GM2 Gangliosidoses

Abstract: By using a sensitive method, we assayed lysocom‐pounds of gangliosides and asialogangliosides in tissues from four patients with GM2 gangliosidosis (one with Sand‐hoff disease and three with Tay‐Sachs disease) and from three patients with GM1 gangliosidosis [one with infantile type (fetus), one with late‐infantile, and one with adult type]. In the brain and spinal cord of all the patients except for an adult GM 1 gangliosidosis patient, abnormal accumulation of the lipids was observed, though the concentration in the fetal tissue was low. In GM2 gangliosidosis, the amounts of lyso GM2 ganglioside accumulated in the brain were similar among the patient with Sandhoff disease and the patients with Tay‐Sachs disease, whereas the concentration of asialo lyso GM2 ganglioside in the brain was higher in the former patient than in the latter patients. By comparing the sphingoid bases of neutral sphingolipids, gangliosides, and lysosphingolipids, it was suggested that lysosphingolipids in the diseased tissue are synthesized by sequential glycosylation from free sphingoid bases, but not by deacyla‐tion of the sphingolipids. Because lysosphingolipids are known to be cytotoxic, the abnormally accumulated lysosphingolipids may well be the pathogenetic agent for the neuronal degeneration in gangliosidoses.