Congenital disorders of glycosylation

Abstract

Congenital (genetic) disorders of glycosylation (CDG) are a rapidly growing disease family, with some 45 members reported since its first clinical description in 1980. Most of these are protein hypoglycosylation diseases, but recently three defects in lipid glycosylation have been identified. Most protein hypoglycosylation diseases are due to defects in the N-glycosylation pathway (16 diseases). The remaining ones affect the O-glycosylation pathway (8 diseases), both the N- and the O-glycosylation pathways, or other pathways (17 diseases). CDG can affect nearly all organs and systems, but there is often an important neurological component. The first-line screening for the N-glycosylation diseases is serum transferrin isoelectrofocusing (IEF), and for the O-glycosylation disorders apo CIII IEF. It has to be stressed that a normal test result does by no means exclude a CDG. In case of an abnormal result and as long as the basic defect has not been elucidated, the disease is labeled CDG-x (CDG-Ix when the transferrin IEF shows a type 1 pattern, and CDG-IIx when it shows a type 2 pattern).

Phosphomannose Isomerase Inhibitors Improve N-Glycosylation in Selected Phosphomannomutase-deficient Fibroblasts

“…The number of cases being diagnosed and the types of CDG are rapidly growing (17,18). Unfortunately, only two CDG types are treatable: CDG-Ib, treatable by mannose therapy, and CDG-IIc, treatable by fucose supplementation (19).…”

A Novel GDP-d-glucose Phosphorylase Involved in Quality Control of the Nucleoside Diphosphate Sugar Pool in Caenorhabditis elegans and Mammals

“…It will therefore be of great interest to screen for mutations in the C15orf58 gene in CDG-I patients for which the basic defect has yet to be elucidated (CDG-Ix patients; Ref. 42). The high expression of GDP-D-Glc phosphorylase in the nervous system suggests a greater vulnerability of this organ to GDP-D-Glc accumulation, which is compatible with the pronounced neurological symptoms that are very commonly observed in CDG-I patients.…”

Hypertrophic Cardiomyopathy With Cardiac Rupture and Tamponade Caused by Congenital Disorder of Glycosylation Type Ia

“…CDGs are a group of genetically heterogenous disorders characterised by dysfunctional production or attachment of glycans to proteins or lipids [5]. Glycoconjugates are important for many processes in the body, including metabolism, cell recognition and adhesion, cell migration, host defense, and antigenicity.…”

“…601785), the enzyme that transforms mannose-6-phosphate to mannose-1-phosphate, an essential step early in the glycosylation pathway [4]. PMM2 deficiency consequently results in hypoglycosylation of numerous glycoproteins, including serum glycoproteins, lysosomal enzymes, and membranous glycoproteins [5].…”