A New Type of Carbohydrate-deficient Glycoprotein Syndrome Due to a Decreased Import of GDP-fucose into the Golgi

• Published in: The Journal of biological chemistry 1999-09, Vol.274 (37), p.25986-25989
• Main Authors: Lübke, Torben, von Figura, Kurt, Körner, Christian, Marquardt, Thorsten
• Format: Article
• Language: English
• Subjects: Biological Transport; Cells, Cultured; Congenital Disorders of Glycosylation - metabolism; Golgi Apparatus - metabolism; Guanosine Diphosphate Fucose - metabolism; Humans
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.37.25986

The fucosylation of glycoproteins was found to be deficient in a patient with a clinical phenotype resembling that of leukocyte adhesion deficiency type II (LAD II). While in LAD II hypofucosylation of glycoconjugates is secondary to an impaired synthesis of GDP-fucose due to a deficiency of the GDP-d-mannose-4,6-dehydratase, synthesis of GDP-fucose was normal in our patient (Körner, C., Linnebank, M., Koch, H., Harms, E., von Figura, K., and Marquardt, T. (1999) J. Leukoc. Biol., in press). Import of GDP-fucose into Golgi-enriched vesicles was composed of a saturable, high affinity and a nonsaturable component. In our patient the saturable high affinity import of GDP-fucose was deficient, while import of UDP-galactose and the activity of GDPase, which generates the nucleoside phosphate required for antiport of GDP-fucose, were normal. Addition ofl-fucose to the medium of fibroblasts restored the fucosylation of glycoproteins. We propose that this new form of carbohydrate-deficient glycoprotein syndrome is caused by impaired import of GDP-fucose into the Golgi.