Wiskott-Aldrich syndrome initially was described in 1937 and then again in 1954 as an X-linked disorder associated with thrombocytopenia, eczema, and recurrent infections. It remained mysterious how different cell lineages could be affected in this syndrome and, more importantly, how the phenotypic features could be so protean. We now know that the features associated with Wiskott-Aldrich syndrome include dysfunction of nearly all effector arms of the immune system, as well as thrombocytopenia with platelet dysfunction. As a consequence of these abnormalities, children and adults with this syndrome have recurrent bleeding, recurrent and significant infections with common and opportunistic organisms, autoimmune disease, and lymphoreticular malignancies. In 1994, the gene that is defective in Wiskott-Aldrich syndrome was identified and found to be a gene with limited homology to any known gene families. In the past 4 years, much has been learned about the role of this protein in cellular function and T-cell responses specifically. This article reviews some recent clinical findings relevant to Wiskott-Aldrich syndrome, the proposed cellular role of this molecule, its biochemical interactions, and genotype-phenotype considerations.
Division of Immunologic and Infectious Diseases, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.