Congenital disorders of glycosylation (CDG)

Abstract

Congenital Disorders of Glycosylation (CDG) comprise permanently expanding group of inherited diseases caused by defects of multiple glycosylation pathways which disturb structure of many glycoconjugates classes. The first patients were described by Jaak Jaeken in 1980, in 1984 simple test was implemented to identify new cases. In 1995, fifteen years later, enzymatic defect was revealed as phosphomannomutase (PMM2) by van Schaftingen group and in 1999 the first classification was proposed. Defects in N-glycosylation pathway are detected most often due to the broad application of the simple screening method, isofocusing (IEF) of serum transferrin. Transferrin normally carries two complex type N-glycans terminated by negatively charged sialic acid. The loss of whole glycan on transferrin molecule or truncation of terminal sugars with sialic acid on glycan result in abnormal, diverse patterns in IEF. The type of pattern suggests location of defect in multistep N-glycosylation pathway and that was the basis of the first CDG classification. New patients identified were classified as CDG of type I or II, for defects in the assembly of dolichol-linked oligosaccharides (LLO) or for defects of subsequent processing steps of glycans bound to protein. Once the gen was found, the newly identified CDG subtype was lined up alphabeticaly as CDG Ia-Iq and CDG-IIa-h. These were mainly defects in the basic N-glycosylation machinery, in glycosyltransferases, glycosidases, sugar transporters but also in the biosynthesis of nucleotide-sugar. With time this nomenclature became inadequate because a novel defects were identified such as: combined Nand Oglycosylation defects due to disturbed vesicular transport (e.g. conserved oligomeric Golgi complex, V-ATPase a2 subunit ), O-mannosylation defects, defects of dolichol biosynthesis and glycolipids glycosylation. Therefore in 2008 the new nomenclature was proposed based on official gen symbol followed by CDG. At present CDG group encompass more than sixty inborn errors of metabolism of which majority are defects of glycoconjugates biosynthesis and small part concern proteins taking part in vesicular transport. Glycoconjugates are ubiquitous molecules in an organism, its function is various and play an important role for many complex processes such growth, differentiation, organ development, signal transduction, immunologic defense and many others. This knowledge well explains extremely broad and diverse clinical spectrum of individual CDG subtypes, from fatal, multisystem disease to milder disease involving only one organ or system. The study of patients with impaired glycosylation have provided already and may provide in the future the new insight into the basic mechanisms of glycosylation. References 1. Hennet T (2012) Biochim Biophys Acta doi:10.1016/j.bbagen.2012.02.001. 2. Jaeken J et al. (2009) Biochim Biophys Acta 1792: 825-826. Session 9. Metabolic Diseases

Cite this paper

@inproceedings{Adamowicz2012CongenitalDO, title={Congenital disorders of glycosylation (CDG)}, author={Maciej Adamowicz and Hieronim Jakubowski}, year={2012} }