Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is an X-linked recessive inherited immune deficiency that affects almost exclusively male patients. Characteristic is the typical symptom triad of microthrombocytopenia, eczema and recurrent infections. Furthermore, there is an increased risk for autoimmune syndromes and malignancies. The disease manifests in infancy, mostly with hemorrhagic symptoms such as petechiae, purpura, gastrointestinal or intracranial haemorrhage. This is followed by acute or chronic eczema as the second characteristic finding.

Due to the combined immune deficiency, most patients frequently suffer from viral and bacterial respiratory, bowel or skin infections, and opportunistic pathogens such as EBV or CMV are also commonly found. About 40% of patients also have autoimmune diseases such as vasculitis, inflammatory bowel disease, arthritides, or hemolytic anemia. WAS patients have a slightly increased risk of developing tumors at any age (especially B-cell lymphomas). The cause of the disease is a mutation in the WAS gene which encodes for the Wiskott-Aldrich syndrome protein expressed exclusively in hematopoietic cells. This protein plays an essential role in the reorganization of the actin cytoskeleton, signal transduction and apoptosis. The actin formation is thus limited, resulting in decreased platelet formation from the megakaryocytes. Clinical and family history can give first clues to the disease. The absence or decreased amount of the WAS protein, and a genetic test confirm the diagnosis.

The only cure is hematopoietic stem cell transplantation, which provides an 80% survival rate. If a donor is missing, the prognosis is altogether unsatisfactory.