To fully understand the etiology of microcytic anemias, we must have an appreciation for two metabolic pathways. First, the formation of hemoglobin, specifically the heme component, and second how iron is acquired, utilized, and stored.
Hemoglobin is made up of two distinct components: heme and globin. Heme production begins during the basophilic normoblast stage of erythropoiesis. Within the cell's mitochondria, glycine and succinyl CoA are acted upon by ALA synthase forming aminolevulinic acid (ALA). This moves into the cytoplasm and is acted on by ALA dehydratase forming porphobilinogen (PBG). Additional enzymes, shown in the diagram, act to form coproporphyrinogen III which is moved back into the mitochondria. Further enzymatic actions result in the formation of protoporphyrin IX which is acted on by ferrochelatase inserting iron into the molecule, forming heme. Heme leaves the mitochondria and is joined to the globin chains in the cytoplasm to create the final hemoglobin molecule.6
Looking at this, we can see the importance of iron and the necessary enzymes to complete this pathway.
- A lack of iron will lead to microcytic anemia resulting in classic iron deficiency anemia.
- A lack of one or more enzymes, or the interference of the pathway completion, results in sideroblastic anemia/porphyria.
- An inability to release ferritin for use can be seen in anemia of chronic inflammation.
6. Keohane, E. M., Otto, C.N., Walenga, J. M. (2019). Rodak's Hematology Clinical Principles and Applications. St. Louis., Elsevier, 6th Edition. Page 95.
