Leukocyte adhesion deficiency II - from A to almost Z

Leukocyte adhesion deficiency (LAD) type II is the second human disorder id entified which involves the adhesion cascade. While in LAD I the integrin f amily is defective, in LAD II the selectin system is involved. The syndrome has been described in only five patients and is transmitted as an autosoma l recessive trait. The infectious episodes and the severity are much milder than those observed in LAD I, and the only persistent clinical symptom is chronic severe periodontitis. Delay separation of the umbilical cord, which is a hallmark for LAD I, was not observed in any of the LAD Il patients. T he exact defect in the system is absence of the SLeX, which is an important ligand for the selectin on the leukocyte leading to a profound defect in l eukocyte rolling, the first step in the adhesion cascade. This causes a mar ked decrease in chemotaxis accompanied by pronounced neutrophilia. Apart fr om the leukocyte defect, these patients suffer from severe growth and menta l retardation and exhibit: the rare Bombay blood group type. The primary de fect in the syndrome is in fucose metabolism, with the absence of all fucos ylated glycans on cell surface membranes. Recently, it is was found that the defect is in a specific transporter of G DP fucose into the Golgi apparatus, and thus no fucosylation process takes place, and no surface expression can be detected. The exact genetic defect in the transporter is still unknown. Four of the patients were of Arabic or igin while the fifth was of Turkish origin. It seems that the primary defec t is somewhat different and, therefore, fucose administration was effective in the Turkish child, but did not show any beneficial results in the patie nts of Arabic origin.