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RESEARCH PRODUCT

Oligosaccharide and Ganglioside Neuraminidase Activities of Mucolipidosis I (Sialidosis) and Mucolipidosis II (I-Cell Disease) Fibroblasts

subject

description

Fibroblasts cultured from the skin of patients with the genetic diseases mucolipidosis I and mucolipidosis II were found deficient in a neuraminidase specific for both an α23 and and α2 6 type of neuraminosyl linkage of sialyl oligosaccharides. Obligate heterozygotes (parents) showed an intermediate activity in mucolipidosis I, but a normal one in mucolipidosis II. The neuraminidase activity of mucolipidosis I fibroblasts towards gangliosides, measured at pH 4.5 in the presence of Triton X-100, was within the range of normal controls with gangliosides Gm3 and GD3, but somewhat diminished with a bovine brain ganglioside preparation. In mucolipidosis II, neuraminidase activity was markedly decreased towards the bovine brain and Gm3 ganglioside substrates, and partially deficient with ganglioside GD3. The results suggest that in mucolipidosis I the degradation of glycoprotein-derived sialyl oligosaccharides is impaired due to the genetic deficiency of an oligosaccharide neuraminidase, whereas the ganglioside catabolism is unaffected. The simultaneous decrease of both oligosaccharide and ganglioside neuraminidase activities in mucolipidosis II fibroblasts is considered to be another example of the multiple lysosomal hydrolase deficiency observed by others in these cells. Our data also suggest that the α23 and α26 oligosaccharide neuraminidase activities are genetically related, yet that they are distinct from the activities towards gangliosides possessing an α23 (GM3) or an α28 (GD3) terminal neuraminosyl linkage.