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 wi th a clinical phenotype resembling that of leukocyte adhesion deficiency ty pe II (LAD II). While in LAD II hypofucosylation of glycoconjugates is seco ndary 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 patie nt (korner, C., Linnebank, NI, Koch, H., Harms, E., von Figura, K., and Mar quardt, T., (1999) J. Leukoc, Biol., in press). Import of GDP-fucose into G olgi-enriched vesicles was composed of a saturable, high affinity and a non saturable component, In our patient the saturable high affinity import of G DP-fucose was deficient, while import of UDP-galactose and the activity of GDPase, which generates the nucleoside phosphate required for antiport of G DP-fucose, were normal, Addition of L-fucose to the medium of fibroblasts r estored 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.