Leukocyte Adhesion Deficiency (LAD) type 1 is an autosomal recessive defect in LFA-1 (CD-18) leading to loss of integrin on phagocytes, predisposing patients to recurrent bacterial infections, absent pus formation, and classically, delayed separation of the umbilicus at birth.
A defect in integrin formation means that neutrophils traveling in the bloodstream are unable to exit at sites of infection, leading to the clinical presentation described. Biopsy of infected skin sites shows absence of neutrophils. LAD type 1 is treated with prophylactic antibiotics and bone marrow transplant for those with especially severe cases.
Cooper et al. report that while the total number of immunodeficiency cases in the United States may be as many as 500,000, only about 50,000 cases are diagnosed annually. Clinicans should suspect primary immunodeficiency if a child has multiple, aggressive infections that recur despite antibiotic treatment, failure to thrive, and a family history of immunodeficiency.
Etzioni reviews different subtypes of LAD, noting that type 1 (deficient CD18 formation) is the most clinically severe, but that types II and III also involve sub-optimal integrin functioning and similar, though less-severe, clinical presentations as LAD type 1.
Illustration A depicts the normal leukocyte-endothelial interactions that occur during vascular inflammation. Thus, a defect in LFA-1 results in dysfunctional leukocyte diapedesis.
Answer 1: Wiskott-Aldrich syndrome is an X-linked immunodficiency characterized by thrombocytopenia at birth and eczema by one year.
Answer 3: DiGeorge syndrome is a deletion on chromosome 22 leading to immunodeficiency, and potential cardiac defects, hypoparathyroidism and cleft plate.
Answer 4: Severe Combined Immunodeficiency (SCID) results from many different genetic mutations including in adenosine deaminase and results in near-complete lack of B- and T-cell function.
Answer 5: Ataxia-telangiectiasia syndrome is a recessive neurodegenerative disease due to ATM on chromosome 11, resulting in immunodeficiency, ataxia, and both cutaneous and ocular telangiectasia.
Cooper MA, Pommering TL, Korányi K. Primary immunodeficiencies. Am Fam Physician. 2003 Nov 15;68(10):2001-8. Review. PubMed PMID: 14655810.
PMID:14655810 (Link to Abstract)
Etzioni A. Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. Adv Exp Med Biol. 2007;601:51-60. Review. PubMed PMID: 17712991
PMID:17712991 (Link to Abstract)