Myelodysplasia and Iron-Transport Deficiency Anemia

In myelodysplastic syndrome, anemia is commonly prominent. The anemia is usually normocytic or macrocytic, and a dimorphic (large and small) population of circulating cells can be present. In some patients with myelodysplastic syndrome, there may be an associated acquired alpha thalassemia (1). (See also Overview of Decreased Erythropoiesis.)

Bone marrow examination shows decreased erythroid activity, megaloblastoid and dysplastic changes, and, sometimes, increased numbers of ringed sideroblasts.

Treatment is directed at the malignancy, and growth factors may be used.

Iron-transport deficiency anemia (atransferrinemia) is exceedingly rare. It occurs when iron cannot move from storage sites (eg, mucosal cells, liver) to the erythropoietic precursors. One well-known form is iron-refractory iron deficiency anemia (IRIDA), caused by germline mutations in the TMPRSS6 (transmembrane serine protease 6) gene, which encodes a transmembrane protein that regulates production of hepcidin, a protein involved in iron absorption (2).

Patients have a microcytic anemia with very low transferrin saturation and are refractory to oral iron. Because hepcidin regulation is defective, hepcidin levels are inappropriately elevated despite iron deficiency.

Treatment of IRIDA is usually with IV iron preparations, although only partial responses typically occur. Prolonged courses of oral iron together with vitamin C may also be attempted.

1. 1. Steensma DP, Gibbons RJ, Higgs DR. Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood. 2005;105(2):443-452. doi:10.1182/blood-2004-07-2792

2. 2. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008;40(5):569-571. doi:10.1038/ng.130