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A genetic cause for iron deficiency
Date:4/13/2008

Although IRIDA is quite rare, the authors believe it might be the extreme end of a broad continuum of disease, since TMPRSS6 mutations varied widely in the five families and caused different degrees of iron deficiency and anemia.

Our observations suggest that more common forms of iron deficiency anemia may have a genetic component, says Andrews.

All patients in the study apparently had recessive mutations, since their parents did not have iron deficiency anemia. The investigators now want to determine whether people with just a single abnormal copy of TMPRSS6 have subtler alterations in iron absorption that might not otherwise have come to the attention of a hematologist.

Although the mechanism is still unknown, deficiency of the TMPRSS6 protein causes the body to produce too much hepcidin, a hormone that inhibits iron absorption by the intestine. Normally, hepcidin is produced to protect the body against iron overload but patients with IRIDA make large amounts of hepcidin even though they are iron deficient. People with this disorder make too much hepcidin, putting the brakes on iron absorption inappropriately, Fleming says.

In addition, patients with TMPRSS6 mutations cannot make new red blood cells efficiently because the iron needed to make them comes from macrophages, and hepcidin causes macrophages to hold on to iron. This explains the patients poor response to intravenous iron the iron is trapped in macrophages and cannot be used for red blood cell production.

The fact that TMPRSS6 regulates hepcidin may open up new avenues for therapy, the researchers say. For example, blocking TMPRSS6 may help patients with iron overload disorders make more hepcidin in order to limit intestinal iron absorption. Conversely, stimulating TMPRSS6 may have therapeutic benefit in certain patients with anemia, particularly those in which hepcidin is overproduced.


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Contact: Jaime Crespo
jaime.crespo@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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