Congenital disorders of glycosylation

Abstract

Glycans are highly diverse carbohydrate moieties that have been selected in evolution to convey dynamic structural and functional properties to the macromolecules to which they are attached. For this reason, correct glycan synthesis is essential for various developmental and physiological processes, particularly in multicellular organisms that use them as communication pathways. The disruption of glycan synthesis frequently results in multisystemic disease with neurological involvement. Congenital disorders of glycosylation (CDGs) have been and will likely remain a rapidly growing group of genetic human diseases that involve different defects in the synthesis or remodelling of N- and O-linked glycans as well as defects in glycosphingolipid and glycosylphosphatidylinositol (GPI) anchor glycosylation. The molecular and clinical characterization of CDGs has enormously contributed to understanding the physiologic roles of the glycosylation machinery and its interaction with other cellular machineries. More than 50 different types of defects have been described and although the first type was described in 1984, CDGs remain widely under-diagnosed or misdiagnosed. This review describes the genetic and biochemical basis of CDGs, as well as the clinical phenotypes and current methods to diagnose them that are ultimately required to establish corrective treatments that are also discussed. © 2012 by Nova Science Publishers, Inc. All rights reserved.