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.
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.
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 is based on the following:
Antibodies to polysaccharide antigens (eg, blood group antigens A and B) may be selectively deficient. Platelets are small and defective, and splenic destruction of platelets is increased, causing thrombocytopenia. Mutation analysis may be used to confirm the diagnosis.
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 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 only established cure is hematopoietic stem cell transplantation, but gene therapy is under study.
Without transplantation, most patients die by age 15; however, some patients survive into adulthood.
Drugs Mentioned In This Article
|Drug Name||Select Trade|