title: A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency.
abstract: Three siblings suffered from an unusual disorder of cyclic vomiting and congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed increased asialo- and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, 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 normoglycosylated transferrin molecules. These findings suggested a defect in the early glycosylation pathway. Phosphomannose isomerase was found to be deficient and the defect was present in leucocytes, fibroblasts, and liver tissue. Phosphomannose isomerase deficiency appears to be a novel glycosylation disorder, which is biochemically indistinguishable from CDG syndrome type I. However, the clinical presentation is entirely different.
authors.affiliation: Department of Metabolic Diseases, University Children's Hospital "Het Wilhelmina Kinderzieken-huis,", Utrecht, The Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: de Koning
authors.forename: L
authors.initials: L
authors.lastname: Dorland
authors.forename: O P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: A M
authors.initials: AM
authors.lastname: Boonman
authors.forename: G J
authors.initials: GJ
authors.lastname: de Jong
authors.forename: W L
authors.initials: WL
authors.lastname: van Noort
authors.forename: J
authors.initials: J
authors.lastname: De Schryver
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: I E
authors.initials: IE
authors.lastname: van den Berg
authors.forename: G J
authors.initials: GJ
authors.lastname: Gerwig
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: B T
authors.initials: BT
authors.lastname: Poll-The
mesh_terms: D000293:Adolescent; D002648:Child; D018981:Congenital Disorders of Glycosylation / Q000145:classification / Q000235:genetics; D005260:Female; D005632:Fructose / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D008358:Mannose / Q000378:metabolism; D008359:Mannose-6-Phosphate Isomerase / Q000172:deficiency* / Q000235:genetics; D017875:Phosphotransferases (Phosphomutases) / Q000032:analysis; D014168:Transferrin / Q000032:analysis
chemical_list: D014168:Transferrin; D005632:Fructose; D008359:Mannose-6-Phosphate Isomerase; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase; D005947:Glucose; D008358:Mannose