A new type of carbohydrate-deficient glycoprotein syndrome due to a decreased import of GDP-fucose into the golgi.

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 of L-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.