Congenital disorders involving defective N-glycosylation of proteins

This review deals with several of the main autosomal recessive congenital d isorders involving defective N-glycosylation of proteins (the addition of g lycans linked to the polypeptide chain by a beta -linkage between the anome ric carbon of N-acetylglucosamine and the amido group of L-asparagine). The se congenital disorders of glycosylation (CDG, previously known as carbohyd rate-deficient glycoprotein syndromes) are a group of multisystemic disease s often involving severe psychomotor retardation. Six distinct variants of CDG in group I (types Ia-If) have been described to date and the defects ha ve been localized to deficiencies in the assembly of the dolichylpyrophosph ate-linked oligosaccharide N-glycan precursor and its transfer to asparagin e residues on the nascent polypeptides. Two variants of CDG group II (types IIa and IIb) have been identified as defects in the processing of protein- bound N-glycans. Hereditary erythroblastic multinuclearity with a positive acidified-serum lysis test (HEMPAS; congenital dyserythropoietic anemia typ e II) presents as a relatively mild dyserythropoietic anemia. The genetic d efect in most cases of HEMPAS is not known, but alpha -3/6-mannosidase II i s involved in at least some patients. Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persist ent leukocytosis and severe mental and growth retardation. LAD II is due to lack of availability of GDP-fucose. The study of these diseases and of rel evant animal models has provided strong evidence that N-glycans are essenti al for normal mammalian development.