title: Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A.
abstract: Carbohydrate-deficient glycoprotein syndrome type 1A (CDGS1A) is an inherited disorder with multisystemic abnormalities resulting from failure to generate sufficient lipid-linked oligosaccharide precursor or to transfer the sugar chain to many glycoproteins. Cultured fibroblasts from these patients have reduced incorporation of mannose into glycoproteins which can be corrected by adding D-mannose to the culture medium. Providing dietary mannose to elevate mannose concentrations in vivo therefore might remedy some of the underglycosylation in the patients. Five children with CDGS1A aged 15 months to 14 y completed a protocol of enteral supplementation with D-mannose 100 mg/kg every 3 h for 9 d. The mean S-mannose level increased from 32 microM (range 22-42 microM) to a trough value of 72 microM (range 39-103 microM). No serious side effects were observed. Surprisingly, the mean serum concentration of four glycoproteins (transferrin, alpha1-antitrypsin, antithrombin, and thyroxine-binding globulin) tended to decrease, and the mean serum concentration of carbohydrate-deficient transferrin (CDT) increased. Furthermore, the initially present abnormal isoforms of these glycoproteins and of protein C became more prominent and/or additional abnormal isoforms appeared. This short-term trial does not support a benefit of mannose to the deficient glycosylation of CDGS1A patients.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Kjaergaard
authors.forename: B
authors.initials: B
authors.lastname: Kristiansson
authors.forename: H
authors.initials: H
authors.lastname: Stibler
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: T
authors.initials: T
authors.lastname: Martinsson
authors.forename: F
authors.initials: F
authors.lastname: Skovby
mesh_terms: D000293:Adolescent; D001774:Blood Chemical Analysis; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D009154:Mutation; D017211:Treatment Failure
chemical_list: D006023:Glycoproteins; D008358:Mannose