Molecular basis of inherited microcytic anemia due to defects in iron acquisitionor heme synthesis

Abstract

Microcytic anemia is the most commonly encounteredanemia in general medical practice. Nutritional iron deficiency and βthalassemia trait are the primary causes inpediatrics, whereas bleeding disorders and anemia ofchronic disease are common in adulthood. Microcytichypochromic anemia can result from a defect in globingenes, in heme synthesis, in iron availability or in ironacquisition by the erythroid precursors. These microcyticanemia can be sideroblastic or not, a trait which reflects theimplications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary microcytic anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcy- tosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these microcytic anemias. © 2009 Ferrata Stori Foundation.