WAS-Related Disorders

Clinical characteristics The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. Diagnosis/testing The diagnosis of a WAS-related disorder is established in a male proband with both congenital thrombocytopenia ( Management Treatment of manifestations: Treatment options depend on an individual's predicted disease burden; hematopoietic cell transplantation (HCT) is the only known curative treatment. Topical steroids for eczema; antibiotics for infected eczema; judicious use of immunosuppressants for autoimmune disease; granulocyte colony stimulating factor (G-CSF) and appropriate antibiotics for neutropenia. Prevention of primary manifestations: Pneumocystis jiroveci (formerly known as Pneumocystis carinii pneumonia, or PCP) prophylaxis with Bactrim® (trimethoprim-sulfamethoxazole) or pentamidine, intravenous immunoglobulin (IVIgG) replacement therapy, routine childhood "non-live" immunizations; judicious use of platelet transfusions for significant bleeding and surgical procedures. Surveillance: Routine monitoring of blood counts and adequacy of IVIgG replacement therapy. Agents/circumstances to avoid: Circumcision of at-risk newborn males who have thrombocytopenia; use of medications that interfere with platelet function. Defer elective procedures until after HCT. Evaluation of relatives at risk: Evaluation of at-risk newborn males so that morbidity and mortality can be reduced by early diagnosis and treatment. Genetic counseling WAS-related disorders are inherited in an X-linked manner. If the mother is a carrier of a WAS pathogenic variant, the chance of transmitting the pathogenic variant in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Males will pass the pathogenic variant to all of their daughters and none of their sons. Female carriers of a WAS pathogenic variant are usually asymptomatic and have no immunologic or biochemical markers of the disorder. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant has been identified in the family.