Carbohydrate-deficient glycoprotein syndromes

Carbohydrate-deficient glycoprotein syndromes are rare, multisystemic disea ses, typically with major nervous system impairment, that are caused by hyp o- and unglycosylation of N-linked glycoproteins. Hence, a biochemical evid ence of this abnormality, like hypoglycosylation of serum transferrin is es sential for diagnosis. Clinically and biochemically, six types of the disea se have been delineated. Three of them are caused by deficiencies of the en zymes that are required for a proper glycosylation of lipid - (dolichol) li nked oligosaccharide (phosphomannomutase or phosphomannose isomerase or alp ha-glycosyltransferase), and one results from a deficiency of Golgi residen t N-acetylglucosaminyltransferase II. In addition one variant of the diseas e has been reported as due to a defective biosynthesis of dolichol iself. T he diseases are heritable but genetics has been established for only two ty pes. Therapy, based on administration of mannose to patients is currently u nder investigation. It benefits patients with deficiency of phosphomannose isomerase. Taking into account the complexity of N-linked glycosylation of proteins more of the disease variants is expected to be found.