Ferrokinetics in the syndrome of familial hypoferremic microcytic anemia with iron malabsorption

Purpose: In 1981, Buchanan and Sheehan described a previously unreported syndrome in three siblings who had iron malabsorption, hypoferremia, and microcytic anemia that did not respond to oral iron and responded only partly to parenteral iron dextran. Ferrokinetic studies were not done in these or subsequently reported patients with this syndrome. It has been postulated that this syndrome of abnormal iron metabolism is analogous to that observed in the mk/mk mouse, which has similar hematologic findings but also has abnormal ferrokinetics. Ferrokinetic studies were performed in one patient to determine whether the abnormality of iron metabolism in the human syndrome is analogous to the mk/mk mouse. Patients and Methods: Two sisters with severe microcytic anemia and iron malabsorption who have had only partial response to parenteral iron have been followed up for 15 years. Ferrokinetic studies with Fe-59 were performed in one sister. Results: Ferrokinetic studies with radio iron were characteristic of iron deficient erythropoiesis (rapid Fe-59 T1/2; rapid, complete incorporation of Fe-59 into erythrocyte hemoglobin). These ferrokinetics differ from those of the mk/mk mouse, which has a missense mutation in Nramp2, a putative iron transporter protein. In these children, once iron enters the plasma its subsequent metabolism (including binding to transferrin), transfer into erythroid bone marrow cells, and subsequent incorporation into erythrocyte hemoglobin are all normal. The defect in these patients appears to be an undefined, novel abnormality that governs mobilization of iron into the plasma from both the intestinal mucosal and reticuloendothelial cells. Despite lifelong severe hypoferremia, the growth, development and intellectual performance of these children, who are teen-agers, are normal.