Studies on Heterogeneity in GM1-Gangliosidosis

The activity of GM1-β-galactosidase in leukocytes and in lymphoblastoid cell lines transformed by Epstein-Barr virus, from five patients with reduced β-galactosidase activity and their parents, was assayed with GM1-ganglioside tritiated in the terminal galactose. Moreover, an analysis of brain ganglioside was performed in two autopsy cases and an affected fetus. The activity of GM1-β-galactosidase in leukocytes and lymphoblastoid cells from four cases was profoundly deficient, and their parents were found to be carriers of obligate heterozygotes. Accordingly, these patients were diagnosed as GM1-gangliosidosis. The activity in leukocytes from a case showed about 6% of the control level and the activity in lymphoblastoid cells was enhanced to a level of about 70% of the control. Although his mother showed the levels of carriers in both samples, the levels of his father were normal. This patient was similar to sialidosis type II with a secondary β-galactosidase defect on the clinical and biochemical findings. However, there are several questionable points at present with regard to the procedures of sialidase assay and further studies into these problems are necessary. On the analys is of the two cases of gangliosides in the brain affected by GM1-gangliosidosis and the brain of the affected fetus, it was suggested that the degree of GM1-ganglioside accumulated was not proportionally related to the level of GM1-galactosidase activity and the content of GM1-ganglioside in the affected fetal brain was similar to the control level