Abnormal glycosphingolipid metabolism in the nervous system of galactosialidosis

Abstract In an autopsy case of galactosialidosis, G M3 , G M2 , G M1 , and G D1a were accumulated in sympathetic and spinal ganglia and grey matter of the spinal cord. Especially, the accumulations of G M3 and G M2 amounted to 41- and 86-fold increases in sympathetic ganglia, respectively, as compared to normal controls. In addition LacCer, GA 2 and GA 1 were accumulated in sympathetic and spinal ganglia. The accumulations of G M3 and G D1a are considered to be the result of defective lysosomal sialidase activity and the accumulation of G M1 , LacCer and GA 1 is also considered to be due to decreased β-galactosidase activity in this disorder. To better understand the possible mechanism of G M2 accumulation, we determined the activity of G M2 synthesizing enzyme (G M3 : UDP-GalNAc transferase), as well as hexosaminidase activity, in sympathetic ganglia, but they did not change. Abnormal ganglioside and neutral glycosphingolipid metabolism, as well as sialyloligosaccharide and sialylglycoprotein metabolism, may be involved in the pathogenesis of this disorder.