Hepcidin plays a central role in the clinical significance of disorders of iron homeostasis. Hepcidin deficiency is the underlying cause of many common genetic iron overload conditions such as hereditary hemochromatosis, thalassemia intermedia, sideroblastic anemia and myelodysplastic syndrome. These disorders are characterized by unrestrained iron absorption that leads to the accumulation of iron in the liver and other tissues that can result in organ failure and sometimes death.
When hepcidin is in excess, iron absorption is inhibited and iron is sequestered in macrophages, leading to iron-restricted erythropoiesis and anemia whose severity is proportional to the level and duration of hepcidin overexpression. If sustained, as in chronic inflammatory diseases such as rheumatoid arthritis and infections, excessive inflammation-induced hepcidin can eventuate in so-called anemia of chronic disease or anemia of inflammation, which is the most common anemia in hospitalized patients. Hepcidin excess can also target the gene encoding serine protease matripase 2 (also called TMPRSS6). Genetic impairment of this enzyme causes iron-refractory iron deficiency anemia (IRIDA) despite having a high normal or high serum hepcidin concentrations in the face of a severe iron deficiency.
Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia.