Leukocyte adhesion deficiency
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| OMIM | 116920 |
|---|---|
| eMedicine | ped/1302 |
| MeSH | D018370 |
Leukocyte adhesion deficiency (abbreviated LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. The disorder is often divided into two separate genotypes called type I and type II, with type II being associated with fewer infections but more developmental delay.
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[edit] Epidemiology
LAD is a rare disease; its estimated prevalence is 1 in 100,000 births. There is no described racial or ethnic predilection.
[edit] Clinical manifestations
LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The defects in adhesion result in poor neutrophil chemotaxis and phagocytosis.
Patients with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, abscesses, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens.
[edit] Molecular defect
The inherited molecular defect in patients with LAD is a deficiency of the β-2 integrin subunit, also called CD18, of the leukocyte cell adhesion molecule, which is found on chromosome 21. This subunit is involved in making three other proteins (LFA-1, CR3, and Mac-1) This basically means that a gene that creates a protein does not function properly. This results in the lack of important molecules which help neutrophils make their way from the blood stream into the infected areas of the body (ie the lungs in pneumonia). Those neutrophils which do manage to make it to the infected areas have a difficult time swallowing (phagocytosing) the bacteria. The bacteria can then proliferate, leading to symptomatic infection). The infection can spread unimpeded and cause serious injury to important tissue.
[edit] Diagnosis
Typically, diagnosis is made after several preliminary tests of immune function are made, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels. Specific diagnosis is made through monoclonal antibody testing for CR3, one of the three complete proteins which fail to form properly as a result of β-2 integrin subunit deficiency.
[edit] Treatment
Once the diagnosis of LAD is made, bone marrow transplantation is the current standard of care. However, some progress has been made in gene therapy, an active area of research.
