There are many forms of
iron storage disease, some hereditary and some acquired. The most common of the hereditary forms is HFE-associated
hemochromatosis, and it is this disorder that is the main focus of this presentation. The body
iron content is regulated by controlling absorption, and studies in the past decade have clarified, in part, how this regulation functions. A 25-amino-acid
peptide hepcidin is up-regulated by
iron and by
inflammation, and it inhibits
iron absorption and traps
iron in macrophages by binding to and causing degradation of the
iron transport protein ferroportin. Most forms of
hemochromatosis results from dysregulation of
hepcidin or defects of
hepcidin or
ferroportin themselves. Hereditary
hemochromatosis was once considered to be very rare, but in the 1970s and 1980s, with the introduction of better diagnostic tests, it was considered the most common disease among Europeans. Controlled epidemiologic studies carried out in the last decade have shown, however, the disease itself actually is rare, and only its genotype and associated biochemical changes that are common. We do not understand why only a few homozygotes develop severe disease. It now seems unlikely that there are important modifying genes, and although alcohol is known to have some effect, excess drinking probably plays only a modest role in determining the
hemochromatosis phenotype. Hereditary
hemochromatosis is readily treated by phlebotomy. Secondary forms of the disease require
chelation therapy, and the recent introduction of effective oral
chelating agents is an important step forward in treating patients with disorders in which
iron overload often proves to be fatal, such as
thalassemia, myelodysplastic
anemias, and dyserythropoietic
anemias. While much has been learned about the regulation of
iron homeostasis in the past decade, many mysteries remain and represent challenges that will keep us occupied for years to come.