Biochemical Characteristics and Diagnosis of the Carbohydrate‐deficient Glycoprotein Syndrome

29 patienxts with a new inherited complex developmental deficiency syndrome—the carbohydrate‐deficient glycoprotein syndrome—were studied biochemically. The most striking biochemical abnormality in these patients is the presence of secretory glycoproteins, that are deficient in their carbohydrate moieties. Serum transferrin shows the most pronounced carbohydrate defect, both quantitatively and qualitatively. Half of this glycoprotein is apparently missing two or four of its terminal trisaccharidcs—sialic acid, galactose and N‐acetylglucosamine—while the carbohydrate core appears to be intact. The abnormal transferrin is also present in the liver. This biochemical alteration is a highly specific marker of the syndrome, which can be diagnosed either qualitatively by isoelectric focusing of serum transferrin or quantitatively by the “carbohydrate‐deficient transferrin” (CDT) assay. In the CDT assay all of these patients have values approximately ten times above the reference level. The unique carbohydrate defect in secretory glycoproteins indicates that this disorder represents a new type of inborn error of glycoprotein metabolism. Studies of eleven enzymes in glycoprotein synthesis and catabolism have not revealed any deficiency of glycosidases or glycosyltransferases. The nature of the transferrin change and the cathepsin assays performed to date may suggest an as yet unidentified degradation abnormality.