The discovery of the gene behind a rare form of inherited iron deficiency may provide clues for new treatments of poor iron absorption in the general population, according to a study released Sunday.
Lack of iron is the most common of all nutritional deficiencies and the leading cause of anemia, which affects nearly a third of the world's population, according the World Health Organisation.
In the developing world, every second pregnant woman and about 40 percent of preschool children are estimated to be anaemic, a condition that contributes to 20 percent of all maternal deaths.
Anemia occurs when there are too few red blood cells in the blood, or when those cells lack the oxygen-carrying protein hemoglobin.
In a study led by Mark Fleming of the Children's Hospital in Boston, Massachusetts, researchers sought to understand why certain children with iron deficiency anemia failed to respond to normally effective oral supplements.
The cause of the rare condition -- called iron-refractory iron-deficiency anemia (IRIDA) -- has been a mystery, but Fleming suspected genes might play a role when he realised that some families had multiple cases.
"After nearly 15 years, we finally had enough families that we could begin to think about positionally cloning the gene for the disorder," he said, referring to a technique for analysing genetic code.
In all of five extended families with more than one chronically iron-deficient member, the researchers found a variety of mutations in a gene called TMPRSS6.
The patients in the study apparently had recessive mutations, since their parents did not have iron deficiency anemia.
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, "putting the brakes on iron absorption inappropriately," Fleming said.
The fact that TMPRSS6 regulates hepcidin may open up new avenues for therapy, the researchers say.
For example, blocking the culprit gene could 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.
The study was published online in the British journal Nature Genetics.