Sideroblastic anemia

Sideroblastic anemia is a group of blood disorders characterized by the bone marrow's inability to incorporate iron into hemoglobin properly, resulting in the accumulation of iron within the mitochondria of developing red blood cells (erythroblasts). These iron-laden erythroblasts, called ring sideroblasts, are the hallmark of the disease when viewed under a microscope. The condition leads to ineffective erythropoiesis (impaired red blood cell production) and can cause anemia of varying severity. Iron overload is a significant complication, as the body continues to absorb iron despite the inability to use it effectively, potentially damaging the liver, heart, and endocrine organs. Sideroblastic anemias can be hereditary (congenital) or acquired. Hereditary forms include X-linked sideroblastic anemia (XLSA), the most common congenital form, caused by mutations in the ALAS2 gene encoding erythroid-specific 5-aminolevulinate synthase, as well as autosomal recessive forms linked to genes such as SLC25A38, GLRX5, and others involved in heme biosynthesis or iron-sulfur cluster assembly. Mitochondrial forms also exist, including those associated with syndromic presentations such as Pearson syndrome and myopathy, lactic acidosis, and sideroblastic anemia (MLASA). Acquired sideroblastic anemias may occur as part of myelodysplastic syndromes (MDS) or secondary to drugs, toxins (lead, alcohol), or nutritional deficiencies (pyridoxine, copper). Key symptoms include fatigue, weakness, pallor, and shortness of breath due to anemia. Iron overload may lead to hepatomegaly, skin hyperpigmentation, diabetes, and cardiac complications over time. Treatment depends on the underlying cause and severity. Pyridoxine (vitamin B6) supplementation is effective in many cases of XLSA, as it serves as a cofactor for ALAS2. Iron chelation therapy may be necessary to manage iron overload. Blood transfusions are used in severe cases, and in some acquired forms, treatment of the underlying condition (e.g., discontinuation of offending agents) may resolve the anemia. Allogeneic hematopoietic stem cell transplantation has been considered in severe refractory cases.

Common questions about Sideroblastic anemia