Catalytically defective ganglioside neuraminidase in mucolipidosis IV

Cultured skin fibroblasts from patients with mucolipidosis IV were found to be deficient in neuraminidase activity toward GD1a and GD1b gangliosides radiolabelled in C8 and C7 analogs of their sialic acid residues. Neuraminidase activities toward 4-methylumbelliferyl-N-acetyl-neuraminic acid, neuraminlactose, and radiolabelled neuraminlactitol, fetuin and alpha 1-acid glycoprotein were within the range of normal controls. Fibroblasts from parents of patients with mucolipidosis IV demonstrated intermediate levels of ganglioside neuraminidase activity and normal levels of glycoprotein neuraminidase activity. The residual acidic neuraminidase activity toward GD1a ganglioside in the patients' fibroblasts did not differ from that of controls in its pH optimum and thermostability, but had an abnormal apparent Km which was about 18 times higher than that of the normal enzyme. These findings suggest that mucolipidosis IV is a ganglioside sialidosis due to a catalytically defective ganglioside neuraminidase.