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Leukocyte adhesion deficiency type I
Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD (see this term) characterized by life-threatening, recurrent bacterial infections.
ORPHA:99842Classification level: Subtype of disorder
LAD-I affects 1 individual per million.
Usually the first signs occur in infancy or early childhood. Patients present recurrent, life-threatening bacterial infections of the skin, mouth, and respiratory tract. Delayed umbilical cord separation is common. Skin infections may evolve into large ulcers. Severe periodontitis is often present later in life and leads to early tooth loss. A lack of swelling, redness, heat, or pus is observed in the area of infection.
LAD-I is caused by mutations in the ITGB2 gene (21q22.3), encoding the beta-2-integrin, CD18, which is essential for firm adhesion of leukocytes to the endothelium. Severity of the disease correlates with the degree of CD18 deficiency.
Diagnosis is based on complete blood counts revealing neutrophilic leukocytosis. Flow cytometric analyses reveal reduced CD18 expression on leukocytes. Genetic analyses of mutations in the ITGB2 gene confirm the diagnosis.
Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease, other primary immunodeficiencies (see these terms) and a leukemoid reaction.
Antenatal diagnosis is possible through biochemical or molecular analysis of chorionic villus cells or amniocytes in affected families for which the mutation has been identified. Flow cytometry can be performed at 20 weeks of gestation.
Transmission is autosomal recessive.
Management and treatment
Management should focus on controlling infections and includes antibiotics. Hematopoietic cell transplantation represents the only cure for LAD-I, but gene therapy may be available in the future.
Prognosis depends on the severity of the disease. Without hematopoietic stem cell transplantation, death in patients with severe LAD-I occurs from infection within the first 2 years of life, whereas patients with a moderate form of the disease have abetter chance of surviving into adulthood. Survival rate after bone marrow transplantation is 75%.