Leukocyte adhesion deficiency

[Vania]

In leukocyte adhesion deficiency, white blood cells (leukocytes) do not function normally, causing frequent soft-tissue infections.

Symptoms of leukocyte adhesion deficiency usually begin during infancy and include frequent infections in soft tissues, such as the gums, skin, and muscles.
Doctors do special blood tests to diagnose the disorder.
Treatment involves antibiotics to prevent infections and transfusions of white blood cells, but stem cell transplantation is the only effective treatment.

(See also Overview of Immunodeficiency Disorders.)
Leukocyte adhesion deficiency is a primary immunodeficiency disorder. It is inherited as an autosomal recessive disorder. That is, two genes for the disorder, one from each parent, are required.
In leukocyte adhesion deficiency, white blood cells are lacking a protein on their surface. As a result, white blood cells are less able to travel to sites of infection and to kill and ingest bacteria and other foreign invaders.
There are three forms of this disorder.

[Julian]

Leukocyte adhesion deficiency results from an adhesion molecule defect that causes granulocyte and lymphocyte dysfunction and recurrent soft-tissue infections.
(See also Overview of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder.)
Leukocyte adhesion deficiency is a primary immunodeficiency disorder that involves phagocytic cell defects. Inheritance is autosomal recessive.
Leukocyte adhesion deficiency is caused by deficiency of adhesive glycoproteins on the surfaces of white blood cells (WBCs); these glycoproteins facilitate cellular interactions, cell attachment to blood vessel walls, cell movement, and interaction with complement fragments. Deficiencies impair the ability of granulocytes (and lymphocytes) to migrate out of the intravascular compartment, to engage in cytotoxic reactions, and to phagocytose bacteria. Severity of disease correlates with degree of deficiency.
Three different types of syndromes have been identified:

Leukocyte adhesion deficiency 1: Deficient or defective beta-2 integrin family
Leukocyte adhesion deficiency 2: Absent fucosylated carbohydrate ligands for selectins
Leukocyte adhesion deficiency 3: Defective activation of all beta integrins (1, 2, and 3)

Type 1 results from mutations in the integrin beta-2 gene (ITGB2), encoding CD18 of beta-2 integrins. Type 2 results from mutations in the glucose diphosphate (GDP)-fucose transporter gene. Type 3 is caused by mutations in the FERMT3 gene (11q13.1), which encodes kindlin-3 in hematopoietic cells.