Congenital disorders of N-glycosylation including diseases associated with O- as well as N-glycosylation defects

The congenital disorders of N-glycosylation (CDG), a steadily increasing group of multi-systemic disorders, have severe clinical implications in infancy and early childhood. The various inborn errors responsible adversely affect N-glycosylation of lysosomal proteins because of either failing assembly of lipid-linked (LL) oligosaccharides (OS) in the endoplasmic reticulum, CDG Type 1, or faulty processing of the asparagines (N)-linked OS in the ER and in the Golgi, CDG Type II. The overlap of phenotypes precludes specific clinical delineation. Isoelectric focusing (IEF) of plasma transferrin remains a valuable, albeit imperfect, screening tool. IEF of plasma ApoC-III protein, introduced O-glycosylation defects that delineated some new CDGs due to mutations of both N- and O-glycosylation. Only CDG-Ib is amenable to treatment with free mannose supplementation. Hence, early specific diagnosis of any one entity is crucial for genetic counseling and elective preventive measures.