Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis

Ann Neurol. 2000 Jun;47(6):776-81.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Brain / metabolism*
  • Brain / pathology
  • Carbohydrate Sequence
  • Child
  • Child, Preschool
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / metabolism
  • Congenital Disorders of Glycosylation / physiopathology*
  • Diagnosis, Differential
  • Endoplasmic Reticulum / metabolism*
  • Epilepsy / physiopathology
  • Female
  • Glucosyltransferases / deficiency*
  • Glucosyltransferases / genetics
  • Glycosylation
  • Homozygote
  • Humans
  • Infant
  • Intellectual Disability / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Molecular Sequence Data
  • Muscles / physiopathology
  • Mutation, Missense
  • Nuclear Family
  • Oligosaccharides / biosynthesis
  • Oligosaccharides / chemistry
  • Polysaccharides / biosynthesis*
  • Polysaccharides / genetics
  • Twins, Monozygotic

Substances

  • Oligosaccharides
  • Polysaccharides
  • Glucosyltransferases
  • dolichol phosphate glucose-dolichol diphosphate oligosaccharide glucosyltransferase