title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
abstract: Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern. Some of the known CDG subtypes were excluded. O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG-7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III, in unclassified CDG-X cases.
authors.affiliation: Department of Biochemical Genetics, Academic Hospital Maastricht, The Netherlands. leo.spaapen@gen.unimaas.nl
authors.forename: L J M
authors.initials: LJ
authors.lastname: Spaapen
authors.forename: J A
authors.initials: JA
authors.lastname: Bakker
authors.forename: S B
authors.initials: SB
authors.lastname: van der Meer
authors.forename: H J
authors.initials: HJ
authors.lastname: Sijstermans
authors.forename: R A
authors.initials: RA
authors.lastname: Steet
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
mesh_terms: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000378:metabolism; D002239:Carbohydrate Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D018981:Congenital Disorders of Glycosylation / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006023:Glycoproteins / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007525:Isoelectric Focusing; D007962:Leukocytes / Q000201:enzymology; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D020033:Protein Isoforms; D035781:Siblings; D014168:Transferrin / Q000096:biosynthesis
chemical_list: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D006023:Glycoproteins; D020033:Protein Isoforms; D014168:Transferrin; D019158:N-Acetylneuraminic Acid