Marked microcytosis and increased transferrin saturation: Think about variants in SLC11A2 (DMT1)

Abstract

Congenital microcytic anemias are rare diseases associated with decreased hemoglobin synthesis and red blood cells of low corpuscular volume. DMT1/NRAMP2 is a highly conserved divalent cation transporter encoded by the SLC11A2 gene, expressed at the membrane of various cells. It ensures ferrous iron absorption from the apical membrane of enterocytes, iron recovery from urine by renal tubules, and acidified endosome uptake after transferrin internalization. Pathogenic DMT1 variants have been described in 10 individuals to date, associated with recessive hypochromic anemia and iron overload. Herein, we report a new variant of SLC11A2 (c.469A>G, p.Ile157Val) compound with known p.Arg416Cys associated with a frankly microcytic anemia and increased transferrin saturation. The clinical picture observed in the patient was exceptionally mild, extending the field of the DMT1 phenotypes to borderline anemias.