A congenital disorder of glycosylation
(previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism
in which N-glycosylation
of a variety of tissue proteins
is deficient or defective. Congenital disorders
of glycosylation are sometimes known as CDG syndromes
. They often cause serious, sometimes fatal, malfunction of several different organ systems
(especially the nervous system
, and intestines
) in affected infants.
They were discovered in the late 1990s. Delineation of types and manifestations has been expanding rapidly, with several new forms described each year since then.
CDG are classified as CDG types I and II (CDG-I and CDG-II), depending on the nature and location of the biochemical defect in the metabolic pathway
relative to the action of oligosaccharyltransferase
- Type I disorders involve disrupted synthesis of the lipid-linked oligosaccharide precursor.
- Type II disorders involve malfunctioning trimming/processing of the protein-bound oligosaccharide chain.
Currently, twelve CDG type-I variants have been identified (CDG-Ia to -Il) and six variants of CDG Type-II have been described (CDG-IIa to -IIe).
The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia
; failure to thrive
; dysmorphic features
(e.g., inverted nipples
and subcutaneous fat pads
; and strabismus
Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic pallor, and reduced rod function on electroretinography.
Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.
No treatment is available for most of these disorders. Mannose
supplementation has produced some benefits in a couple of the Type I subtypes. Several synthetic glycoconjugate compounds have been synthesized and are being tested for therapeutic efficacy.