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Discovery of the genetic cause of a rare
disorder known as iron-refractory iron
deficiency anemia (IRIDA) may give clues about more common forms of iron
deficiency. Mark Fleming, MD, interim pathologist-in-chief at Children's, and
pediatric hematologist Nancy Andrews, MD, PhD, formerly of Children's and now dean of Duke University School of Medicine, conducted a genetic search after seeing a number of children whose condition did not respond to oral or
intravenous supplements, and for which no other explanation could be found. Many of the children had affected siblings.
Studies of five extended families revealed a variety of mutations in the gene TMPRSS6. The resulting deficiency of TMPRSS6 protein causes the body to make too much hepcidin, inhibiting intestinal
iron absorption and interfering with
erythropoiesis. Because the mutations
varied widely and caused different degrees of iron deficiency and anemia, doctors Fleming and Andrews believe that IRIDA might represent the extreme end of a
continuum, and that more common forms of iron deficiency anemia might also have a
genetic component.
The findings also suggest that
stimulating TMPRSS6 may benefit
certain patients with anemia, particularly those in whom hepcidin is overproduced. Conversely, blocking TMPRSS6 may help patients with iron overload disorders make more hepcidin, reducing intestinal iron absorption. (Nature Genetics, April 13, 2008)
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