title: Human beta-galactosidase and alpha-neuraminidase deficient mucolipidosis: genetic complementation analysis of the neuraminidase deficiency.
abstract: Human beta-galactosidase and alpha-neuraminidase deficient mucolipidosis [ML(gal-neur-)] is an inherited lysosomal enzymopathy which recently was designated as a sialidosis. We analyzed the neuraminidase deficiency of this disorder with genetic complementation analyses using a heterokaryon enrichment procedure. The genetic defects of two apparent variants of this disorder complemented the defects of the neuraminidase deficiency diseases, sialidosis I and mucolipidosis I, resulting in the restoration of neuraminidase activity in heterokaryons. The neuraminidase deficiency, therefore, may not be the primary defect in ML(gal-neur-) and is not an appropriate test for determining carrier status. The clinical and biochemical characteristics of this disorder suggest that a post-translational or processing event for these enzymes may be defective. The defect, however, is different from I-cell disease and pseudo-Hurler polydystrophy, two disorders of post-translational lysosomal enzyme biosynthesis, since complementation studies demonstrated recovery of intracellular beta-galactosidase and alpha-neuraminidase levels in heterokaryons. The lack of human beta-galactosidase expression in man-mouse somatic cell hybrids formed from fibroblasts of the infantile onset type disorder suggests that the defect is not corrected by the mouse genome. The ML(gal-neur-) disorder therefore appears to be a distinct subtype of the inherited neuraminidase deficiencies in which the defect mat occur in a post-translational or regulatory step which coordinately affects the expression of lysosomal beta-galactosidase and alpha-neuraminidase.
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000201:enzymology; D006580:Genetic Carrier Screening; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006801:Humans; D006822:Hybrid Cells; D007787:Lactose Intolerance / Q000145:classification / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D009081:Mucolipidoses / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D009439:Neuraminidase / Q000172:deficiency*; D014176:Protein Biosynthesis
chemical_list: D009439:Neuraminidase