secondary hemochromatosis

Secondary hemochromatosis occurs when iron accumulation results from acquired causes rather than inherited defects in iron metabolism. The most common cause is transfusional iron overload, typically seen in patients requiring chronic transfusions (thalassemia major, sickle cell disease, myelodysplastic syndromes). Each unit of blood contains ~250mg of iron, and the body can only eliminate 1-2mg daily, leading to progressive accumulation. Other causes include chronic hemolytic anemia with ineffective erythropoiesis (β-thalassemia intermedia), excessive oral iron supplementation, chronic liver disease (especially alcoholic liver disease and viral hepatitis), and rarely, dietary iron overload in certain populations. The pathophysiology differs from primary hemochromatosis because hepcidin regulation may initially be appropriate, but the system becomes overwhelmed. Iron deposition patterns may also differ, with transfusional overload often affecting the reticuloendothelial system first before parenchymal organs. Clinical manifestations mirror primary hemochromatosis: hepatomegaly, cirrhosis, diabetes mellitus, cardiomyopathy, arthropathy, and hypogonadism. Diagnosis involves elevated serum ferritin and transferrin saturation, but genetic testing for HFE mutations is negative. Treatment focuses on addressing the underlying cause when possible and iron removal via phlebotomy or chelation therapy (deferoxamine, deferiprone, deferasirox).