Iron-deficiency anemia secondary to mutations in genes controlling hepcidin

The discovery of the peptide hormone hepcidin in 2001 has shed light on the control of iron metabolism. Studies in animal models over the past few years have demonstrated its key role in regulating iron homeostasis. It was found that hepcidin deficiency leads to iron overload, and that its overexpression leads to severe iron-deficiency anemia. Since then, other genes regulating hepcidin expression have been discovered, and defects in them mostly resulted in iron overload. In 2008, a new gene, TMPRSS6, was identified that encodes a negative regulator of hepcidin expression. This discovery has been of great relevance because TMPRSS6 is the first gene regulating hepcidin, mutations in which cause chronic iron-deficiency anemia. Recently, genome-wide association studies identified common TMPRSS6 variants associated with hematological parameters, suggesting that TMPRSS6 is crucial in the control of iron homeostasis and normal erythropoiesis.