Congenital Disorders of Glycosylation (CDG): A Rapidly Expanding Group of Neurometabolic Disorders

The recently delineated Congenital Disorders of Glycosylation (CDG), formerly known as Carbohydrate-Deficient Glycoprotein syndromes, are a group of inherited multisystem diseases due to defective N-glycosylation of proteins. Protein glycosylation is a frequent posttranslational modification and many secreted and membranous proteins have covalently bound carbohydrate units. These serve a variety of functions, allowing correct folding of the proteins, their protection against proteases and modulation of their biological activities [[17]]. The biosynthesis of N-linked oligosaccharides is elaborate and numerous glycosyltransferases are involved, attaching sugars to a growing lipid-linked oligosaccharide chain, stepwise. The donors are either nucleotide-activated or dolichol phosphate-linked sugars for these transfer reactions. Finally, the completed structure (Gluc3Man9GlcNAc2) is transposed en bloc within the endoplasmatic reticulum (ER). It is then attached to an asparagine residue of a nascent protein via the oligosaccharyltransferase complex. In the Golgi compartment, several glycosidases can remodel the oligosaccharide chain into a more complex structure by removal of mannose residues and the addition of N-acetylglucosamine, galactose, fucose and sialic acid residues [[13]].