Description

The defect of leukocyte adhesion type 1 (LAD-1) is a form of LAD (see this term) characterized by recurrent bacterial infections that can lead to death. One person per million is affected. Generally, the first signs appear during childhood or early childhood. Bacterial infections affect the skin, the oral cavity and the respiratory tract, and, in the first case, can develop into severe ulcers. The delay in detachment of the umbilical cord is characteristic. Serious periodontitis is common in adults, which may result in premature loss of teeth. There is no swelling, redness, heat, or pus at the site of infection. LAD-1 is caused by mutations in the ITGB2 gene (21q22.3), which encodes beta-2-integrin, CD18, which plays a fundamental role in the adhesion of leucocytes to the endothelium. Transmission is autosomal recessive. The severity of the disease correlates with the degree of CD18 deficiency. The diagnosis is based on a complete blood count, which reveals neutrophilic hyperleukocytosis. Flow cytometry allows to show a reduced expression of CD18 on leukocytes. Confirmation of the diagnosis is based on the analysis of mutations in the ITGB2 gene. The differential diagnosis arises with IRAK-4 deficiency, dominated autosomal hyper-IgE syndrome, chronic granulomatosis, other primitive immunodeficiencies (see these terms) and the leukemoid reaction. Prenatal diagnosis is based on biochemical and molecular analysis on chorionic villi or amniocytes in affected families in which mutations have been identified. Flow cytometry can be performed at the 20th week of gestation. Management is based on infection control with antibiotic administration. The only possible treatment for LAD-1 is hematopoietic cell transplantation, but in the future gene therapy could become an alternative. The prognosis depends on the severity of the disease. People with severe LAD-1 who do not receive hematopoietic stem cell transplantation usually die in the first two years of life due to infections; subjects with milder forms are more likely to reach adulthood. The survival rate after bone marrow transplantation is 75%.

External Information

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