The Wiskott–Aldrich syndrome (WAS), caused by mutations in the WAS gene, is a complex and diverse disorder with X-linked inheritance. This review focuses on recent developments in the understanding of its basic pathophysiology, diverse clinical phenotypes and optimal patient management including novel therapies.
The protein encoded by the WAS gene is a multifunctional signaling element expressed in immune and hematopoietic cells that plays a critical role in cytoskeletal reorganization, immune synapse formation and intracellular signaling. The type of specific mutation, its location within the gene and its effect on protein expression play a major role in determining an individual patient's clinical phenotype. Recent clinical observations and molecular studies have created a sophisticated picture of the disease spectrum. The improved outcome of stem cell transplantation from related and unrelated matched donors and promising early results from the first clinical gene therapy trial have added new therapeutic options for these patients.
Classic WAS, X-linked thrombocytopenia and X-linked neutropenia are caused by WAS gene mutations, each having a distinct pattern of clinical symptoms and disease severity. New developments in the understanding of these syndromes and novel therapeutic options will have a major impact on the treatment of individuals with WAS mutations.
aDepartment of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital der Ludwig-Maximilians-Universität, Munich, Germany
bThe Manton Center for Orphan Disease Research and the Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
cDepartment of Pediatrics, University of Washington, and Seattle Children's Research Institute, Center for Immunity and Immunotherapy, Seattle, Washington, USA
Correspondence to Dr med. Hans D. Ochs, MD, Professor of Pediatrics, Jeffrey Modell Chair of Pediatric Immunology Research, Seattle Children's Hospital Research Institute, Research Center for Immunity and Immunotherapy, 1900 Ninth Avenue, 7th Floor, Seattle, WA 98101, USA Tel: +1 206 987 7318; fax: +1 206 987 7310; e-mail: firstname.lastname@example.org, email@example.com