title: Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis.
abstract: We report on 8 patients with a recently described novel subtype of congenital disorder of glycosylation type Ic (CDG-Ic). Their clinical presentation was mainly neurological with developmental retardation, muscular hypotonia, and epilepsy. Several symptoms commonly seen in CDG-Ia such as inverted nipples, abnormal fat distribution, and cerebellar hypoplasia were not observed. The clinical course is milder overall, with a better neurological outcome, than in CDG-Ia. The isoelectric focusing pattern of serum transferrin in CDG-Ia and CDG-Ic is indistinguishable. Interestingly, beta-trace protein in cerebrospinal fluid derived from immunoblot analysis of the brain showed a less pronounced hypoglycosylation pattern in CDG-Ic patients than in CDG-Ia patients. Analysis of lipid-linked oligosaccharides revealed an accumulation of Man9GlcNAc2 intermediates due to dolichol pyrophosphate-Man9GlcNAc2 alpha-1,3 glucosyltransferase deficiency. All patients were homozygous for an A333V mutation.
authors.affiliation: Department of Pediatics, Heinrich-Heine University Düsseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Grünewald
authors.forename: T
authors.initials: T
authors.lastname: Imbach
authors.forename: K
authors.initials: K
authors.lastname: Huijben
authors.forename: M E
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.forename: A
authors.initials: A
authors.lastname: Verrips
authors.forename: J B
authors.initials: JB
authors.lastname: de Klerk
authors.forename: H
authors.initials: H
authors.lastname: Stroink
authors.forename: J F
authors.initials: JF
authors.lastname: de Rijk-van Andel
authors.forename: J L
authors.initials: JL
authors.lastname: Van Hove
authors.forename: U
authors.initials: U
authors.lastname: Wendel
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: T
authors.initials: T
authors.lastname: Hennet
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D019943:Amino Acid Substitution; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002240:Carbohydrate Sequence; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D003937:Diagnosis, Differential; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004827:Epilepsy / Q000503:physiopathology; D005260:Female; D005964:Glucosyltransferases / Q000172:deficiency* / Q000235:genetics; D006031:Glycosylation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000503:physiopathology; D020125:Mutation, Missense; D009679:Nuclear Family; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry; D011134:Polysaccharides / Q000096:biosynthesis* / Q000235:genetics; D014430:Twins, Monozygotic
chemical_list: D009844:Oligosaccharides; D011134:Polysaccharides; D005964:Glucosyltransferases; C054676:dolichol phosphate glucose-dolichol diphosphate oligosaccharide glucosyltransferase