-transparent.png){kind=logo}
Carbohydrate-deficient glycoprotein syndrome (CDGS) is a rare metabolic disorder presenting in infancy with severe neurologic involvement and variable multisystemic abnormalities. Diagnosis relies upon the detection of abnormal serum glycoprotein isoforms on isoelectric focusing (IEF) gels. Carbohydrate structural analyses were performed on the N-linked oligosaccharides of serum alpha 1-antitrypsin (alpha-1AT) from two Danish children with classical type I CDGS. Following preparative gel electrophoresis of alpha-1AT isoforms, oligosaccharide charge and monosaccharide composition analyses revealed increased glycosylation heterogeneity in CDGS compared with normal alpha-1AT. CDGS alpha-1AT isoforms bore N-glycans co-migrating with monosialylated standards, while normal alpha-1AT oligosaccharides co-migrated with both mono- and disialylated standards. While the monosaccharide contents of normal alpha-1AT isoforms were relatively uniform, those of CDGS alpha-1AT isoforms varied widely, and many were relatively mannose enriched. The mannose-rich oligosaccharides of CDGS alpha-1AT were not typical oligomannose structures since they were not released by endo-beta-N-acetylglucosaminidase H (endo H) digestion. Metabolic labelling of CDGS fibroblasts with [3H]mannose showed lower than normal intracellular total mannose, free mannose and phosphorylated mannose species, as well as diminished [3H]mannose incorporation into dolichol-linked and protein-linked oligosaccharides. In addition, the glycans liberated from CDGS dolichol-linked oligosaccharides were significantly truncated compared with those from normal fibroblasts. These data suggest that our type I CDGS patients produce abnormal N-linked oligosaccharides due to impaired biosynthesis of dolichol-oligosaccharide precursors.
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
August 1998,
The Journal of clinical investigation,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
November 1994,
Seikagaku. The Journal of Japanese Biochemical Society,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
January 1997,
Advances in pediatrics,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
December 1995,
Nihon rinsho. Japanese journal of clinical medicine,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
January 1996,
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
November 1994,
Ugeskrift for laeger,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
April 1994,
Biochemical and biophysical research communications,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
February 2000,
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
April 1991,
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke,
D M Krasnewich, and
G D Holt, and
M Brantly, and
F Skovby, and
J Redwine, and
W A Gahl
August 1997,
Biochemical and molecular medicine,
