Snapshot A 1-year-old boy is brought to the emergency room for bloody diarrhea. He has a history of recurrent ear infections, diarrhea, and atopic dermatitis. He had an older sibling who died of a pulmonary infection at a young age. On physical exam, there is dried blood in his nares bilaterally and bleeding at intravenous puncture sites. Additionally, purpura is noted on his arms. Laboratory results show marked thrombocytopenia requiring platelet transfusions. Immunoglobulin levels show decreased IgG and IgM but increased IgE and IgA. Introduction Clinical definition primary immunodeficiency disorder of B- and T-cells WATER Wiskott Aldrich Thrombocytopenic purpura Eczema Recurrent infections etiology Pathogenesis loss of cellular and humoral response Genetics X-linked recessive mutation in WAS gene encoding Wiskott-Aldrich Syndrome protein (WASp) T-cells are unable to recognize actin cytoskeleton impaired phagocytosis and chemotaxis Presentation Symptoms/physical exam ranges from isolated thrombocytopenia to classic Wiskott-Aldrich Syndrome with recurrent infections, eczema, and thrombocytopenia recurrent bacterial, viral, fungal infections frequency increases with age bacterial agents Streptococcus pneumonia, Haemophilus influenza, and Neisseria meningitides viral agents varicella and CMV fungal infections Candida albicans thrombocytopenia recurrent bleeding, especially in first days of life petechiae purpura easy bruising hematemesis epistaxis hematuria chronic eczema hepatosplenomegaly common Studies Diagnostic testing studies ↓ number of T- and B-cells ↓ to normal IgG and IgM ↑ IgE and IgA thrombocytopenia Differential Severe combined immunodeficiency distinguishing factor similarly presents with recurrent bacterial infections unlike Wiskott-Aldrich syndrome, there is no thrombocytopenia or risk of bleeding Transient hypogammaglobulinemia of infancy distinguishing factor does not extend beyond infancy DIAGNOSIS Diagnostic criteria gene sequence analysis of WAS essential to confirm diagnosis Treatment Management approach mainstay of treatment is to treat infections with antibiotics and treat bleeding with platelet transfusions hematopoietic cell transplant is the most effective therapy First-line hematopoietic stem cell transplantation indications all patients as early as possible intravenous immunoglobulin (IVIG) indications all patients platelet transfusions indication bleeding from thrombocytopenia Complications Increased risk of autoimmune diseases malignancies (lymphomas and leukemias), usually fatal infections Chronic eczema superinfection Prognosis Reduced life expectancy Bleeding is the main cause of death