Wiskott-Aldrich syndrome results from a combined B- and T-cell defect and is characterized by recurrent infection, atopic dermatitis, and thrombocytopenia.

Inheritance is X-linked recessive. Wiskott-Aldrich syndrome is caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASP), a cytoplasmic protein necessary for normal B- and T-cell signaling. Because B- and T-cell functions are impaired, infections with pyogenic bacteria and opportunistic organisms, particularly viruses and Pneumocystis jirovecii, develop.

The first manifestations are often hemorrhagic (usually bloody diarrhea), followed by recurrent respiratory infections, eczema, and thrombocytopenia. Cancers, especially Epstein-Barr virus lymphomas and acute lymphoblastic leukemia, develop in about 10% of patients > 10 yr.

Diagnosis

Diagnosis is based on tests showing impaired antibody responses to polysaccharide antigens, cutaneous anergy, partial T-cell immunodeficiency, elevated IgE and IgA levels, low IgM levels, and low or normal IgG levels. Antibodies to polysaccharide antigens (eg, blood group antigens A and B) may be selectively deficient. Platelets are small and defective, and splenic destruction of platelets is increased, causing thrombocytopenia. Mutation analysis may be used.

Treatment

Treatment is splenectomy, continuous antibiotics, IV immunoglobulin, and bone marrow transplantation. Without transplantation, most patients die by age 15; however, some patients survive into adulthood.

Last full review/revision September 2008 by Rebecca H. Buckley, MD