|
A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids 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. The most common subtype is CDG-Ia (also referred to as PMM2-CDG) where the genetic defect leads to the loss of phosphomannomutase 2, the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate. ==History== The first CDG patients (twin sisters) were described in an abstract in the medical journal ''Pediatric Research'' in 1980 by Jaeken et al. 〔 Jaeken, J., Vanderschueren-Lodeweyckx, M., Casaer, P., Snoeck, L., Corbeel, L., Eggermont, E., and Eeckels, R. (1980) Pediatr Res 14, 179〕 Their main features were psychomotor retardation, cerebral and cerebellar atrophy and fluctuating hormone levels (''e.g.''prolactin, FSH and GH). During the next 15 years the underlying defect remained unknown but since the plasmaprotein transferrin was underglycosylated (as shown by ''e.g.'' ''isoelectric focusing''), the new syndrome was named carbohydrate-deficient glycoprotein syndrome (CDGS).〔Jaeken, J., and Carchon, H. (1993) The carbohydrate-deficient glycoprotein syndromes: an overview. J Inherit Metab Dis. 16, 813-20.〕 Its "classical" phenotype included psychomotor retardation, ataxia, strabismus, anomalies (fat pads and inverted nipples) and coagulopathy. In 1994, a new phenotype was described and named CDGS-II.〔Jaeken, J., Schachter, H., Carchon, H., De Cock, P., Coddeville, B. and Spik, G. (1994) Arch. Dis. Childhood 71, 123-127〕 In 1995, Van Schaftingen and Jaeken showed that CDGS-I (now CDG-Ia or PMM2-CDG) was caused by the deficiency of the enzyme phosphomannomutase. This enzyme is responsible for the interconversion of mannose-6-phosphate and mannose-1-phosphate, and its deficiency leads to a shortage in GDP-mannose and dolichol (Dol)-mannose (Man), two donors required for the synthesis of the lipid-linked oligosaccharide precursor of N-linked glycosylation. In 1998, Niehues et al. published a new CDG syndrome, CDG-Ib, which is caused by mutations in the enzyme metabolically upstream of PMM2, phosphomannose isomerase (PMI).〔Niehues, R., Hasilik, M., Alton, G., Körner, C., Schiebe-Sukumar, M., Koch, H.G., Zimmer, K.P., Wu, R., Harms, E., Reiter, K., von Figura, K., Freeze, H.H., Harms, H.K., Marquardt, T. Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. (1998) J. Clin. Invest. 101, 1414-20.〕 In this paper, the authors also described a functional therapy for CDG-Ib, alimentary mannose. The characterization of new defects took up speed and several new Type I and Type II defects were delineated.〔Haeuptle, M.A., and Hennet, T. Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. (2009) Hum Mutat 30, 1628-41.〕 In 2012, Need et al. published the first case of a congenital disorder of deglycosylation, which resulted from mutations in the NGLY1 gene. A 2014 study of NGLY1 deficient patients found similarities with traditional congenital disorders of glycosylation. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「congenital disorder of glycosylation」の詳細全文を読む スポンサード リンク
|