Regulation of iron homeostasis

Hepcidin disorders of iron metabolism result in iron overload rather than iron deficiency. They are attributable to mutations that affect the regulation of intestinal iron absorption and body iron distribution. The prominence of mutations that cause iron loading, rather than iron deficiency, can probably be explained by the fact that humans live in an iron-rich environment, and the body has developed strategies to limit iron absorption rather than to enhance it.

Several years ago, it was widely believed that there was only one major genetic disorder leading to iron overload. It is now clear that there are many genetic iron overload disorders. They can be generally classified as hemochromatosis disorders (i.e. iron deposition in parenchymal cells) or siderosis disorders (i.e. deposition of iron in reticuloendothelial macrophages). The known disorders and their genetic causes are listed in Table 13.1.

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