Red Blood Cell Disorders Pediatric Research and Clinical Trials

Children’s Hospital Boston has some of the world’s best hematologists. Members of our team authored the major academic textbooks used for the evaluation of all kinds of red cell disorders, including:

Discovering a gene for a rare form of inherited iron deficiency

Iron deficiency is the most common nutritional deficiency and the leading cause of anemia in the United States. Most cases are easily reversed with oral iron supplements, but over the years, Mark Fleming, MD, DPhil, chief of Pathology at Boston Children's Hospital, and Nancy Andrews, MD, PhD, formerly an associate in Hematology at Children's and now dean of Duke University School of Medicine, had been referred a number of children with iron deficiency anemia who didn't respond to oral supplements, and only poorly to intravenous iron.

The cause of their rare condition, termed iron-refractory iron-deficiency anemia, was a mystery. The children all had good diets, and none had any condition that might interfere with iron absorption or cause chronic blood loss, the most common causes of iron deficiency. All had evidence of anemia from a very early age, and many also had siblings with iron deficiency anemia. Seeing reports of several similarly afflicted families in the medical literature, Drs. Fleming and Andrews were convinced that genetics was a factor.

Drs. Fleming and Andrews, experts in iron metabolism, studied five extended families with more than one chronically iron-deficient member. They found a variety of mutations in a gene called TMPRSS6 (transmembrane serine protease S6) in all of these families, as well as several patients without a family history of the disorder.

The discovery of a gene for a rare form of inherited iron deficiency may provide clues to iron deficiency in the general population, particularly iron deficiency that doesn't respond to iron supplements.