title: Glycoprotein lysosomal storage disorders: alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency.
abstract: Glycoproteinoses belong to the lysosomal storage disorders group. The common feature of these diseases is the deficiency of a lysosomal protein that is part of glycan catabolism. Most of the lysosomal enzymes involved in the hydrolysis of glycoprotein carbohydrate chains are exo-glycosidases, which stepwise remove terminal monosaccharides. Thus, the deficiency of a single enzyme causes the blockage of the entire pathway and induces a storage of incompletely degraded substances inside the lysosome. Different mutations may be observed in a single disease and in all cases account for the nonexpression of lysosomal glycosidase activity. Different clinical phenotypes generally characterize a specific disorder, which rather must be described as a continuum in severity, suggesting that other biochemical or environmental factors influence the course of the disease. This review provides details on clinical features, genotype-phenotype correlations, enzymology and biochemical storage of four human glycoprotein lysosomal storage disorders, respectively alpha- and beta-mannosidosis, fucosidosis and alpha-N-acetylgalactosaminidase deficiency. Moreover, several animal disorders of glycoprotein metabolism have been found and constitute valuable models for the understanding of their human counterparts.
authors.affiliation: Laboratoire de Chimie Biologique, UMR 8576 CNRS (UMR 111 CNRS), Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France. jean-claude.michalski@univ-lille1.fr
authors.forename: J C
authors.initials: JC
authors.lastname: Michalski
authors.forename: A
authors.initials: A
authors.lastname: Klein
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology*; D004195:Disease Models, Animal; D005645:Fucosidosis / Q000201:enzymology* / Q000235:genetics; D006026:Glycoside Hydrolases / Q000172:deficiency; D006596:Hexosaminidases / Q000172:deficiency*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D008363:alpha-Mannosidosis / Q000201:enzymology* / Q000235:genetics; D048809:alpha-N-Acetylgalactosaminidase
chemical_list: D006026:Glycoside Hydrolases; D006596:Hexosaminidases; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase