Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients

Leukocyte adhesion deficiency type II is an autosomal recessive syndrome ch aracterized by generalized reduction of L-fucose in glycoconjugates; the sp ecific molecular defect is still undefined. The most important clinical sym ptoms include severe growth and mental retardation and severe immunodeficie ncy. Patients from two ethnic groups have been reported, i.e. Arab and Turk ish. We have observed that GDP-L-fucose transport into Golgi vesicles was s pecifically impaired in an Arab patient, with a significant reduction of th e V-max but no significant differences in the K-m from control and parents. GDP-L-fucose transport showed simple saturation kinetics in all samples. T ransport of UDP-galactose, UDP-N-acetylglucosamine, and CMP-sialic acid was comparable into vesicles from the Arab patient, parents, and control. Thes e kinetic parameters probably account for the failure to obtain any clinica l and biochemical response to fucose therapy in Arab patients. This contras ts both with the distinctive kinetic properties of GDP-L-fucose transport a nd with the success of fucose therapy, which have been recently reported in one patient of Turkish origin. Accordingly, the biochemical properties of CIDP-L-fucose transport into the Golgi are consistent with different varian ts of leukocyte: adhesion deficiency type II that an probably the result of different molecular defects.