Congenital disorder of glycosylation

A congenital disorder of glycosylation 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, muscles, and intestines) in affected infants.

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History

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.^[1]

Classification

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).

Presentation

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; 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.^[2]

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.^[3]

Treatment

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.

See also

• Inborn error of metabolism

References

1. ^ Freeze HH (2006). "Genetic defects in the human glycome". Nat. Rev. Genet. 7 (7): 537-51. doi:10.1038/nrg1894. PMID 16755287.
2. ^ Jensen H, Kjaergaard S, Klie F, Moller HU (2003). "Ophthalmic manifestations of congenital disorder of glycosylation type 1a". Ophthalmic Genet. 24 (2): 81–8. PMID 12789572.
3. ^ Sun L, Eklund EA, Chung WK, Wang C, Cohen J, Freeze HH (2005). "Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia". J. Clin. Endocrinol. Metab. 90 (7): 4371-5. doi:10.1210/jc.2005-0250. PMID 15840742.