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: S Grünewald, T Imbach, K Huijben, M E Rubio-Gozalbo, A Verrips, J B de Klerk, H Stroink, J F de Rijk-van Andel, J L Van Hove, U Wendel, G Matthijs, T Hennet, J Jaeken, R A Wevers
• Journal: Annals of neurology (Ann Neurol) Vol. 47 Issue 6 Pg. 776-81 (Jun 2000) ISSN: 0364-5134 [Print] United States
• PMID: 10852543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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