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congenital disorders of glycosylation

Monday 6 October 2003

Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins.

The Congenital Disorders of Glycosylation (CDG) are a collection of over 20 inherited diseases that impair protein N-glycosylation.

The clinical appearance of CDG patients is quite diverse making it difficult for physicians to recognize them.

A simple blood test of transferrin glycosylation status signals a glycosylation abnormality, but not the specific defect.

An abnormal trasferrin glycosylation pattern suggests that the defect is in either genes that synthesize and add the precursor glycan (Glc(3)Man(9)GlcNAc(2)) to proteins (Type I) or genes that process the protein-bound N-glycans (Type II).

Type I defects create unoccupied glycosylation sites, while Type II defects give fully occupied sites with abnormally processed glycans.

These types are expected to be mutually exclusive, but a group of patients is now emerging who have variable coagulopathy and hypoglycemia together with a combination of Type I and Type II transferrin features.


- congenital disorder of glycosylation type I (CDG-Is or CDG1s)

  • congenital disorder of glycosylation type Ia (CDG-Ia or CDG1A)
  • congenital disorder of glycosylation type Ib (CDG-Ib or CDG1B) (MIM.602579) (12872847)

- congenital disorder of glycosylation type II (CDG-IIs or CDG2s)

Type I CDGs (CDG1s) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin.


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