Wiskott-Aldrich Syndrome

What is Wiskott-Aldrich syndrome?

Wiskott-Aldrich syndrome is a rare disorder characterized by eczema, abnormal immune system function, and a reduced ability to form blood clots. Wiskott-Aldrich syndrome primarily affects males.

What are the symptoms of Wiskott-Aldrich syndrome?

The following are the signs and symptoms of Wiskott-Aldrich syndrome:

• Increased tendency to bleed caused by a significantly reduced number of platelets
• Recurrent bacterial, viral, and fungal infections
• Eczema of the skin
• Increased risk of developing severe autoimmune disease
• Increased incidence of malignancy (cancer), particularly lymphoma or leukemia

What causes Wiskott-Aldrich syndrome?

Wiskott-Aldrich syndrome results from an X-linked genetic defect in the Wiskott-Aldrich syndrome protein (WASp). The gene resides on Xp11.22-23, and its expression is limited to cells of non-erythroid hematopoietic lineage. The type of mutation to the WASp gene correlates with the degree of severity of the disease. Those mutations that led to the production of a truncated protein cause significantly more symptoms than those with a missense mutation but normal-length WASp.

How is Wiskott-Aldrich syndrome diagnosed?

Diagnosis is based on family history, physical examination, and laboratory investigations that reveal severe thrombocytopenia. This severe thrombocytopenia is characterized by reduced platelet size with a usually normal number of megakaryocytes, as well as altered antibody production. Absent or decreased WAS protein levels and genetic testing confirm the diagnosis.

What are the available treatments for Wiskott-Aldrich syndrome?

Currently, the only cure available for Wiskott-Aldrich syndrome is hematopoietic stem cell transplantation (HSCT). Gene therapy, still experimental to date, may also prove an effective approach for patients lacking a suitable donor. Immunoglobulin replacement therapy and oral antibiotics prevent infections. Severe eczema requires treatment with topical or short-term systemic steroids. Treatments that could weaken the immune system (steroids, splenectomy, immunosuppressive agents) should be used with the highest caution by trained medical staff. Agonists of the thrombopoietin receptors (such as romiplostim and eltrombopag) can be used to increase the platelet count in severe refractory thrombocytopenia cases that are awaiting HSCT or gene therapy.

Where can I find out more about Wiskott-Aldrich syndrome?

• NIH
• Immune Deficiency Foundation
• Orphanet