The leukocyte adhesion defiency syndromes are immune deficiencies that exhibit impaired adhesion of leukocytes, severe leukocytosis, and recurrent infections. So far, around 350 cases have been described. The disease is already manifested in infancy or early childhood.
Three different defects in the stages of leukocyte adhesion have been elucidated. The defect results from the migration of leukocytes from the vessels to the site of infection, for which the adhesion of the leukocytes to the endothelium is necessary.
LAD-I is most common and is characterized by life-threatening, recurrent bacterial infections. They occur in the skin, respiratory tract and mouth, whereby infections of the skin can develop into large ulcerations. Already after birth a delayed detachment of the umbilical cord is characteristic. In later life, periodontitis often occurs leading to premature tooth loss. Despite infections, every sign of inflammation is missing. The LAD-1 is based on a mutation in the ITGB2 gene (21q22.3), which codes for the beta-2 integrin CD18. This is essential for the adhesion of leukocytes to the endothelium.
LAD-II are intellectual deficits, severely retarded growth, recurrent infections and leukocytosis. The reason for this is a mutation in the SLC35C1 gene (11p11.2), which codes for the guanosine 5'-diphosphate (GDP) -fucose transporter.
LAD-III is a serious bacterial infection associated with severe bleeding. The cause is found in a mutation in the FERMT3 gene (11q13.1), which codes for Kindlin-3 hematopoietic cells.
Inheritance is autosomal recessive in all three cases.