Background: Thalassemia represents one of the most common inherited hemoglobinopathies worldwide, with a particularly high prevalence in pediatric populations across the Mediterranean, Middle East, and South Asia. The disease is characterized by impaired synthesis of globin chains, leading to ineffective erythropoiesis, chronic hemolysis, iron overload, and multiorgan complications. Pathophysiology: In children, ẞ-thalassemia major is the most severe form, manifesting with profound anemia, bone marrow expansion, and growth retardation. The underlying molecular defects involve diverse genetic mutations affecting ẞ-globin chain production. Secondary complications, including endocrine dysfunction, cardiac failure, and hepatic damage, are largely attributable to transfusion-related iron overload. Diagnosis: Advances in diagnostic approaches, including molecular genetic testing and next-generation sequencing, now allow earlier and more precise detection, complementing traditional hematological indices and hemoglobin electrophoresis. Prenatal and neonatal screening programs have played a pivotal role in reducing disease incidence in high-risk regions. Treatment Advances: While regular blood transfusions and iron chelation therapy remain the mainstay of management, recent innovations have transformed the therapeutic landscape. Improved oral iron chelators have enhanced compliance and outcomes, while hematopoietic stem cell transplantation offers a potential cure in selected pediatric patients. Emerging therapies, including gene addition/editing strategies and novel pharmacologic agents such as luspatercept, hold promise for altering the natural course of disease. Conclusion: Thalassemia in children remains a major global health challenge; however, rapid advances in molecular diagnostics, supportive care, and curative strategies are reshaping prognosis. Future directions focus on expanding curative options, optimizing individualized treatment, and improving access to novel therapies in resource-limited settings.
