Public release date: 6-Feb-2008
Researchers discover the origin of hereditary hemochromatosis, a common iron overload disorder, is a genetic defect in the liver
Much less widely known than the dangerous consequences of iron deficiencies is the fact that too much iron can also cause problems. The exact origin of the genetic iron overload disorder hereditary hemochromatosis [HH] has remained elusive. In a joint effort, researchers from the European Molecular Biology Laboratory [EMBL] and the University of Heidelberg, Germany, have now discovered that HH is a liver disease. They report in the current issue of Cell Metabolism that the disorder develops when a crucial gene is lacking in liver cells.
“For a long time scientists thought of HH as a disease of the intestine, because this is where iron uptake actually takes place,” says Matthias Hentze, Associate Director of EMBL. “Our research now reveals that the crucial point is actually the liver and explains why HH patients suffer from increased iron absorption.”
HFE encodes a protein that is likely involved in transmitting signals about the current iron contents of the body to liver cells. In response to these signals, the liver cells make a special iron hormone, hepcidin, that is released into the blood stream and reduces iron uptake in the intestine.
“HFE influences hepcidin expression through a series of intermediate molecules, but when the HFE gene is mutated the result is that less hepcidin is produced. This in turn means iron uptake in the intestine cannot be limited as effectively and an overload develops,” says Martina Muckenthaler, professor at the University of Heidelberg.