title: [Fabry disease (alpha-galactosidase deficiency)].
abstract: Fabry disease is an X-linked glycosphingolipid storage disorder resulting from a deficiency of lysosomal alpha-galactosidase (alpha-Gal; EC 3.2.1.22). Classical form patients, with clinical manifestations of generalized angiopathy of early onset, usually show no detectable alpha-Gal activity. There are also atypical form patients with residual alpha-Gal activity and late onset cardiomyopathy without other systemic manifestations. We identified a number of alpha-Gal gene mutations including partial deletions and point mutations. They were heterogeneous and more than half of them were missense mutations. Various missense mutants were expressed in COS-1 cells. Two groups have been identified; one expressing a mutant enzyme without catalytic activity, and the other expressing a catalytically active but unstable mutant enzyme. The latter was restored in patient cells by the addition of substrate analogues. The molecular genetic and biochemical analysis for Fabry disease will provide us with significant informations on the pathogenesis and the possibility of the therapeutic approach for this disease.
authors.affiliation: Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science.
authors.forename: T
authors.initials: T
authors.lastname: Okumiya
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D002220:Carbamazepine / Q000627:therapeutic use; D000795:Fabry Disease / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009154:Mutation; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D018712:Analgesics, Non-Narcotic; D002220:Carbamazepine; D000519:alpha-Galactosidase