Congenital Disorders of Glycosylation (CDG): Update and Perspectives

Congenital Disorders of Glycosylation (CDG) are a rapidly growing family of genetic and mostly multisystem diseases caused by defects in the biosynthesis of the glycan moiety of glycoconjugates such as glycoproteins. Since the description of the first patients by Jaeken et al. in 1980, 23 defects have been identified in N- and O-protein glycosylation: 18 defects in N- or N- and O-glycosylation (12 glycan assembly defects: CDG-Ia to CDG-IL; 6 glycan processing defects: CDG-IIa to CDG-IIf) and 5 defects in O-glycosylation. There is a rapidly growing number of patients with a putative CDG in whom the known defects have been excluded (CDG-x). This review focuses on recent developments in the field including advances in the biochemical and molecular diagnosis of CDG and new features of known CDG. It also deals with the identification of new protein glycosylation disorders, of the first lipid glycosylation disorder, and of the emerging group of hyperglycosylation disorders. Finally, we speculate about future developments.