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 of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder.)
Wiskott-Aldrich syndrome is a primary immunodeficiency disorder that involves combined humoral and cellular immunity deficiencies.
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).
Because B- and T-cell functions are impaired, infections with pyogenic bacteria and opportunistic organisms, particularly viruses and Pneumocystis jirovecii, develop. Infections with varicella zoster virus and herpes simplex virus are common.
Довідковий матеріал загального характеру
1. Shcherbina A, Rosen FS, Remold-O'Donnell E: Pathological events in platelets of Wiskott-Aldrich syndrome patients. Br J Haematol 106(4):875–883, 1999. doi:10.1046/j.1365-2141.1999.01637.x
Symptoms and Signs of Wiskott-Aldrich Syndrome
The first manifestations are often hemorrhagic (usually bloody diarrhea), followed by recurrent respiratory infections, eczema, and thrombocytopenia.
Cancers, especially B-cell lymphomas (EBV+) and acute lymphocytic leukemia, develop in about 10% of patients > 10 years.
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. 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 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, 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).
Without aggressive intervention with transplantation or gene therapy, most patients die by age 15; however, some patients survive into adulthood.
Довідковий матеріал щодо лікування
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
