Carbohydrate-deficient glycoprotein syndrome type II

The carbohydrate-deficient glycoprotein syndromes (CDGS) are a group of aut osomal recessive multisystemic diseases characterized by defective glycosyl ation of N-glycans. This review describes recent findings on two patients w ith CDGS type II. In contrast to CDGS type I, the type II patients show a m ore severe psychomotor retardation, no peripheral neuropathy and a normal c erebellum. The CDGS type II serum transferrin isoelectric focusing pattern shows a large amount (95%) of disialotransferrin in which each of the two g lycosylation sites is occupied by a truncated monosialo-monoantennary N-gly can. Fine structure analysis of this glycan suggested a defect in the Golgi enzyme UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransfe rase II (GnT II; EC 2.4.1.143) which catalyzes an essential step in the bio synthetic pathway leading from hybrid to complex N-glycans. GnT LT activity is reduced by over 98% in fibroblast and mononuclear cell extracts from th e CDGS type II patients. Direct sequencing of the GnT II coding region from the two patients identified two point mutations in the catalytic domain of GnT LT, S290F (TCC to TTC) and H262R (CAC to CGC). Either of these mutatio ns inactivates the enzyme and probably also causes reduced expression. The CDG syndromes and other congenital defects in glycan synthesis as well as s tudies of null mutations in the mouse provide strong evidence that the glyc an moieties of glycoproteins play essential roles in the normal development and physiology of mammals and probably of all multicellular organisms. (C) 1999 Elsevier Science B.V. All rights reserved.