Congenital Disorder of Glycosylation
| Classification according to ICD-10 | |
|---|---|
| E77.8 | Other disorders of glycoprotein metabolism |
| ICD-10 online (WHO version 2019) | |
CDG means Congenital Disorders of Glycosylation , which literally means congenital diseases of glycosylation . Another common name for these disorders is dystroglycanopathy . Glycosylation is the connection of sugar chains with different biomolecules such as proteins ( proteins ) and fats. There are different ways of attaching sugar chains to proteins. The known diseases of glycosylation mainly concern N-glycosylation (N for the amino group of the amino acid asparagine), in which sugar chains (N-glycans) are synthesized to the amino acid asparagine in a specific sequence with other amino acids. The initial steps in building up the N-glycans take place in the endoplasmic reticulum , on a lipid anchor located in the membrane of the ER , the dolichol . Only then is the glycan transferred to the protein. The N-glycans are completed in the Golgi apparatus .
In the so-called O-glycosylation (O for the hydroxyl group of the amino acid), sugars are mainly synthesized using the amino acids serine and threonine ; the O-glycans are built up almost exclusively in the Golgi apparatus. It is estimated that around 1% of all genes encode proteins that are involved in glycosylation processes.
Sugar chains play an essential role on numerous proteins, for example the blood group characteristics A, B and O consist of different sugar chains. Numerous other proteins are linked with sugar chains and are accordingly referred to as glycoproteins . Since the function of many glycoproteins is limited if the sugar chains are missing or faulty, CDG diseases often lead to numerous failures. However, there are also diseases that only affect one organ or a cell system.
The first CDG was characterized molecularly and biochemically in 1995 by the Belgian pediatrician J. Jaeken (see Jaeken syndrome ). Since then, numerous other disorders of glycosylation have been described as separate disease entities. More than 17 CDGs have already been described and new diseases are being discovered in quick succession.
The clarification of the new CDG made it necessary to rename the diseases from the former Carbohydrate-Deficient Glycoprotein Syndrome (CDG Syndrome, CDGS) to Congenital Disorders of Glycosylation in 2000. The abbreviation CDG was retained.
The new classification is based on the intracellular localization of the molecular defect. Disturbances in the structure of the oligosaccharide structure in the endoplasmic reticulum are referred to as CDG-I, disturbances in the modification of the oligosaccharides in the endoplasmic reticulum and Golgi apparatus as CDG-II . The discovered CDG are named with small letters in the order of their discovery (CDG Ia, description 1995, CDG Ib, description 1998, etc.). All CDG known to date have an autosomal recessive inheritance.
literature
- HH Freeze: Towards a therapy for phosphomannomutase 2 deficiency, the defect in CDG-Ia patients. In: Biochim Biophys Acta. (2009); 1792 (9), pp. 835-840. PMID 19339218 ; PMC 2783247 (free full text)
