A NOVEL DISORDER OF N-GLYCOSYLATION DUE TO PHOSPHOMANNOSE ISOMERASE DEFICIENCY

Three siblings suffered from an unusual disorder of cyclic vomiting an d congenital hepatic fibrosis, Serum transferrin isoelectric focusing showed increased asialo-and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphoman nomutase, which is deficient in most patients with type I CDG syndrome , was found to be normal in all three patients. Structural analysis of serum transferrin revealed nonglycosylated, hypoglycosylated, and nor moglycosylated transferrin molecules. These findings suggested a defec t in the early glycosylation pathway. Phosphomannose isomerase was fou nd to be deficient and the defect was present in leucocytes, fibroblas ts, and liver tissue. Phosphomannose isomerase deficiency appears to b e a novel glycosylation disorder, which is biochemically indistinguish able from CDG syndrome type I. However, the clinical presentation is e ntirely different. (C) 1998 Academic Press.