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Wiskott-Aldrich Syndrome

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Reviewed/Revised Jan 2023
View PATIENT EDUCATION

Wiskott-Aldrich syndrome is an immunodeficiency disorder that involves a combined B- and T-cell defect and is characterized by recurrent infection, eczema, 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. Thrombocytopenia likely occurs due to various reasons, including increased platelet clearance, ineffective thrombocytopoiesis, and/or decreased platelet survival (1 General reference Wiskott-Aldrich syndrome is an immunodeficiency disorder that involves a combined B- and T-cell defect and is characterized by recurrent infection, eczema, and thrombocytopenia. (See also Overview... read more ).

General reference

Symptoms and Signs of Wiskott-Aldrich Syndrome

The first manifestations are often hemorrhagic (usually bloody diarrhea), followed by recurrent respiratory infections, eczema, and thrombocytopenia.

Diagnosis of Wiskott-Aldrich Syndrome

  • Immunoglobulin levels

  • Platelet count and volume assessment

  • White blood cell function tests (eg, neutrophil chemotaxis, T-cell function)

Diagnosis of Wiskott-Aldrich syndrome is based on the following:

  • Decreased T-cell count and function

  • Elevated IgE and IgA levels

  • Low IgM levels

  • Low or normal IgG levels

  • Decreased natural killer cell cytotoxicity

  • Impaired neutrophil chemotaxis

Antibodies to polysaccharide antigens (eg, blood group antigens A and B) may be selectively deficient; quantitative immunoglobulin response to polysaccharide vaccines (eg, pneumococcal vaccine) is usually measured. Platelets are small and defective, and splenic destruction of platelets is increased, causing thrombocytopenia Overview of Platelet Disorders Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more Overview of Platelet Disorders . Mutation analysis may be used to confirm the diagnosis if there is clinical and laboratory evidence of Wiskott-Aldrich syndrome.

Genetic testing is recommended for 1st-degree relatives.

Because risk of lymphoma and leukemia is increased, a complete blood count with differential is usually done every 6 months. Acute changes in symptoms related to B-cell dysfunction require more in-depth evaluations.

Treatment of Wiskott-Aldrich Syndrome

  • Supportive care using prophylactic immune globulin, antibiotics, and acyclovir

  • For symptomatic thrombocytopenia, platelet transfusion and rarely splenectomy

  • Hematopoietic stem cell transplantation

  • Gene therapy

Treatment of Wiskott-Aldrich syndrome is prophylactic antibiotics and immune globulin Replacement of missing immune components Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more to prevent recurrent bacterial infections, acyclovir to prevent severe herpes simplex virus infections, and platelet transfusions to treat hemorrhage. If thrombocytopenia is severe, splenectomy can be done, but it is usually avoided because it increases risk of septicemia.

The most well-established cure is hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more , but gene therapy is under study. A recent small study of lentiviral hematopoietic stem/progenitor cell gene therapy in 8 patients with Wiskott-Aldrich syndrome followed for up to 7.6 years demonstrated resolution of severe infections and eczema and a decrease in autoimmune and bleeding disorders in all of the patients (1 Treatment reference Wiskott-Aldrich syndrome is an immunodeficiency disorder that involves a combined B- and T-cell defect and is characterized by recurrent infection, eczema, and thrombocytopenia. (See also Overview... read more ).

Without aggressive intervention with transplantation or gene therapy, most patients die by age 15; however, some patients survive into adulthood.

Treatment reference

  • 1. Magnani A, Semeraro M, Adam F, et al: Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome [published correction appears in Nat Med 2022 Oct;28(10):2217]. Nat Med 28(1):71–80, 2022. doi:10.1038/s41591-021-01641-x

Drugs Mentioned In This Article

Drug Name Select Trade
Pneumovax 23, Pnu-Imune-23 , Prevnar, Prevnar 13 , Prevnar 20, VAXNEUVANCE
Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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