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Iron metabolism in heterozygotes for hemoglobin E (HbE), -thalassemia 1, or β-thalassemia and in compound heterozygotes for HbE/β-thalassemia^1,2,3

¹ From the Laboratory for Human Nutrition, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland (MBZ, CZ, and RFH); the Thalassemia Research Center, Institute of Science and Technology for Research and Development (SF and PS) and the Institute of Nutrition (PW, SG, and KJ), Mahidol University, Salaya, Nakon Pathom, Thailand; and the Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (TT and JLM)

Background: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons.

Objective: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for β-thalassemia, -thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/β-thalassemia heterozygotes.

Design: In Thai women (n = 103), red blood cell indexes, iron status, non-transferrin-bound iron, and growth differentiation factor 15 were measured, and body iron was calculated. Fractional iron absorption was measured from meals fortified with isotopically labeled (⁵⁷Fe) Fe sulfate, and iron utilization was measured by the infusion of (⁵⁸Fe) Fe citrate.

Results: Iron utilization was 15% lower in -thalassemia 1 or β-thalassemia heterozygotes than in controls. When corrected for differences in serum ferritin, absorption was significantly higher in the - and β-thalassemia groups, but not the HbE heterozygotes, than in controls. HbE/β-thalassemia compound heterozygotes had lower iron utilization and higher iron absorption and body iron than did controls. Nontransferrin-bound iron and growth differentiation factor 15 were higher in the compound heterozygotes, but not in the other groups, than in the controls.

Conclusions: In -thalassemia 1 and β-thalassemia heterozygotes with ineffective erythropoesis, dietary iron absorption is not adequately down-regulated, despite a modest increase in body iron stores. In populations with a high prevalence of these traits, a program of iron fortification could include monitoring for possible iron excess and for iron deficiency.