Leukocyte Adhesion Deficiency (LAD) Syndromes

Key words Disease name and included diseases Definition Epidemiology Genetics Diagnostic criteria Differential diagnosis Etiology Clinical description Diagnostic methods Prenatal diagnosis Management and treatment References Abstract The hallmarks of leucocyte adhesion deficiency (LAD) are defects in the leucocyte adhesion process, marked leukocytosis and recurrent infections. These molecular and clinical manifestations result from an impaired step in the inflammatory process, namely, the emigration of leukocytes from the blood vessels to sites of infection, which requires adhesion of leukocytes to the endothelium. In the last 20 years, three distinctive defects in the leucocyte adhesion cascade, involving several precise ordered steps such as rolling, integrin activation and firm adhesion of the leukocytes have been described. While LAD I and II are clearly autosomal recessive disorders, the mode of inheritance of LAD III is still not clear. LAD I is due to structural defects in the integrin molecule, preventing a firm adhesion to occur. In LAD II, the primary genetic defect is in a specific Golgi GDP-fucose transporter that leads to absence of the selectin ligand on the leukocyte and a defective rolling. LAD III or LADI/variant, which was last described, is due to defects in the integrin activation process. All three syndromes are very rare, LAD I being more frequent than LAD II and III, with LAD I being described in more than 300 patients worldwide and LAD II and III in less than 10 children each. The most important focus should be to control infections. Treatment includes antibiotics and in many cases bone marrow transplantation.