Leukocyte adhesion deficiency

Infobox_Disease
Name = Leukocyte-adhesion deficiency


Caption =
DiseasesDB =
ICD10 =
ICD9 =
ICDO =
OMIM = 116920
MedlinePlus =
eMedicineSubj = ped
eMedicineTopic = 1302
MeshID = D018370

Leukocyte-adhesion deficiency (abbreviated LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections.cite web |url=http://www.merck.com/mmpe/sec13/ch164/ch164k.html |title=Leukocyte Adhesion Deficiency: Immunodeficiency Disorders: Merck Manual Professional |accessdate=2008-03-01 |format= |work=] 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.

Epidemiology

LAD is a rare disease, with an estimated prevalence of 1 in 100,000 births. There is no described racial or ethnic predilection.

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.

Genetics

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, Integrin alphaXbeta2, and Mac-1/CD3) This basically means that the gene creates a non-functioning protein. 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 phagocytosing (swallowing) the bacteria. The bacteria can then proliferate, leading to symptomatic infection. The infection can spread unimpeded and cause serious injury to important tissue.

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.

Treatment

Once the diagnosis of LAD is made, bone marrow transplantation is the current standard of care. [cite journal |author=van Vliet DN, Brandsma AE, Hartwig NG |title=Leukocyte-adhesion deficiency - a rare disorder of inflammation |journal=Ned Tijdschr Geneeskd. |volume=145 |issue=50 |pages=2496–2500 |year=2004 |pmid=15638198 ] However, some progress has been made in gene therapy, an active area of research.

ee also

* Leukocyte adhesion cascade

External links

* [http://www.primaryimmune.org Immune Deficiency Foundation]
* [http://www.ladinfo.org Leukocyte Adhesion Deficiency Web Site]

References