Congenital sideroblastic anemia: Unravelling molecular pathogenesis and advancing precision therapeutics

Congenital sideroblastic anemia (CSA) is a rare and heterogeneous disorder characterized by the presence of ring sideroblasts within the bone marrow. The underlying pathogenesis of CSA is predominantly attributed to defects in three major pathways: heme biosynthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis. The advent of next-generation sequencing technologies has facilitated the identification of numerous pathogenic gene mutations, offering valuable insights into the molecular mechanisms underlying CSA. Emerging therapeutic strategies, such as vitamin B6 supplementation, iron chelation therapy, hematopoietic stem cell transplantation, innovative agents including luspatercept, and gene-editing techniques, exhibit promising potential in managing anemia and reducing iron overload. This review summarizes genetic advances, pathophysiological mechanisms, and evolving treatments, underscoring the shift toward precision medicine in CSA management.