A REVIEW ON TARGETTING WISKOTT ALDRICH SYNDROME (WAS)- INNOVATIONS IN TREATMENT AND CARE

Ramsharan, *Ashok Kumar, Nidhi Chaudhary, Abhishek Bhardwaj, Dr. Amandeep Singh

Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency disorder characterized by the classic triad of microthrombocytopenia, eczema, and recurrent infections. Caused by mutations in the WAS gene, which encodes the Wiskott-Aldrich Syndrome protein (WASp), this condition disrupts actin cytoskeleton organization, impairing the function of hematopoietic cells and leading to immune dysregulation. Clinical manifestations range from classic WAS to milder forms such as X-linked thrombocytopenia (XLT) and X-linked neutropenia (XLN). Patients often face severe infections, autoimmune complications, and malignancies, contributing to high morbidity and mortality. Diagnosis relies on clinical evaluation, laboratory findings, and genetic confirmation. Despite advancements in molecular diagnostics and a clinical scoring system that guides management, delayed diagnosis remains a challenge, particularly in low-resource settings. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, though accessibility is limited in developing countries. Emerging therapies, such as autologous gene-modified HSCT using lentiviral vectors, offer promising alternatives with improved safety profiles, but require further validation for long-term efficacy. Management of WAS includes infection prevention with intravenous immunoglobulin (IVIG) and prophylactic antibiotics, immunosuppressive therapies for autoimmune manifestations, and supportive care for thrombocytopenia. Splenectomy, while effective for platelet count improvement, poses risks of infection, especially post-HSCT. This study provides a comprehensive overview of the pathophysiology, clinical spectrum, diagnosis, and current and emerging treatment strategies for WAS, with a special focus on challenges in resource-limited regions like India. It underscores the critical need for increased awareness, early diagnosis, infrastructure development, and equitable access to advanced therapies. Future directions include improved gene therapy modalities, immune modulation strategies, and global collaboration to enhance outcomes for affected individuals.