Wiskott–Aldrich Syndrome: Clinical and Immunological Diagnosis Despite Negative Genetic Testing

Introduction X-linked thrombocytopenia (XLT) is a milder variant within the Wiskott–Aldrich syndrome (WAS) spectrum, an immunodeficiency characterized by thrombocytopenia with small platelets, eczema, and recurrent infections. Unlike classic WAS, XLT predominantly presents with hematologic symptoms and less immunological involvement. Diagnosis can be challenging, especially in early stages or when genetic tests are inconclusive. Case Report An 8-month-old male infant with a family history of a maternal uncle who died from an unspecified hematologic disease presented with bicytopenia at 2 months of age that did not improve despite iron supplementation and transfusions. Bone marrow aspirate revealed primary thrombocytopenia with suspected immune etiology. Steroid treatment was initiated, resulting in partial improvement. By 6 months, the patient developed eczema and diaper area dermatitis without severe infections. Laboratory studies showed low platelet volume, anemia, decreased IgM, and poor isohemagglutinin response. Prophylaxis was started and breastfeeding was discontinued. Whole exome sequencing revealed no pathogenic variants. Due to refractory thrombocytopenia, flow cytometry was performed, demonstrating decreased expression of WAS protein (WASp) in CD3+ T lymphocytes, supporting the diagnosis. The patient remains stable and is currently enrolled in a hematopoietic stem cell transplant protocol. Discussion Functional assays such as protein expression analysis are essential to establish diagnosis, even when exome sequencing is negative. Clinical and functional findings guide diagnosis, management, and prognosis.