Decreased availability of GDP-L-fucose in a patient with LAD II with normal GDP-D-mannose dehydratase and FX protein activities

Leukocyte adhesion deficiency type II (LAD II) is caused by a disorder in the metabolism of GDP-L-fucose, which causes hypofucosylation of glycoconjugates, This study analyzes a newly identified LAD II patient who shows the same severe hypofucosylation of glycoconjugates as the other described patients, However; in vitro assays of cytosolic extracts from leukocytes and fibroblasts of the patient demonstrated a normal GDP-L-fucose biosynthesis from GDP-D-mannose, Analysis of the two enzymes involved in the pathway, GDP-D-mannose 4,6-dehydratase and FX protein, revealed normal numbers of transcripts without any detectable mutations within the coding regions of either gene. In contrast to previously published observations [Sturla et al, (1998) FEES Lett. 429, 274-278], the major pathway of GDP-L-fucose synthesis can be normal in LAD II.