(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency 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 .)
Wiskott-Aldrich syndrome is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves combined humoral and cellular immunity deficiencies Combined humoral and cellular immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more .
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 ).
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 Chickenpox Chickenpox is an acute, systemic, usually childhood infection caused by the varicella-zoster virus (human herpesvirus type 3). It usually begins with mild constitutional symptoms that are followed... read more and herpes simplex virus Herpes Simplex Virus (HSV) Infections Herpes simplex viruses (human herpesviruses types 1 and 2) commonly cause recurrent infection affecting the skin, mouth, lips, eyes, and genitals. Common severe infections include encephalitis... read more are common.
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 Acute Lymphoblastic Leukemia (ALL) Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer; it also strikes adults of all ages. Malignant transformation and uncontrolled proliferation of an abnormally differentiated... read more , develop in about 10% of patients > 10 years.
Diagnosis of Wiskott-Aldrich Syndrome
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 . 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
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 n 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.
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|