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Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients

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Abstract

Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients. Optimal treatment has yet to be determined. We identified five patients from four independent families displaying the IRIDA picture with truncating biallelic mutations in TMPRSS6, one of which is novel. Liver iron determined by superconducting quantum interference device biosusceptometry ranged from 390 to 720 µg Fe/g wet weight (normal range 100–500; n = 3). Intestinal iron absorption (12 and 32 %, normal range 10–50; n = 2) and 59Fe erythrocyte incorporation after ingestion of 59Fe (57 and 38 %, normal range 70–90; n = 2) were inadequately low for iron-deficient anemic individuals. Baseline serum erythropoietin was elevated or borderline high in four patients. Administration of recombinant human erythropoietin (rhEPO) at up to 273 and 188 U/kg body weight/week alone did not improve anemia or result in a decrease of urinary hepcidin in two individuals. In conclusion, the ability of exogenous rhEPO to increase hemoglobin level appears to be impaired in IRIDA.

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Abbreviations

BMP:

Bone morphogenetic proteins

BW:

Body weight

DMT1:

Divalent metal transporter 1

HJV:

Hemojuvelin

IRIDA:

Iron refractory iron deficiency anemia

RES:

Reticuloendothelial system

rhEPO:

Recombinant human erythropoietin

SELDI-TOF:

Surface-enhanced laser desorption ionization time-of-flight

SMAD:

Son of mothers against decapentaplegic

SQUID:

Superconducting quantum interference device

TMPRSS6:

Transmembrane protease, serine 6

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Acknowledgments

M.U.M acknowledges funding by eRARE-BMBF (HMA-IRON) and the Dietmar-Hopp-Stiftung.

Conflict of interest

The authors have no competing interests.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University Medical Center Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Kai Lehmberg, Regine Grosse, Peter Nielsen, Florian Oyen, Reinhard Schneppenheim & Gritta E. Janka

  2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital, Heidelberg, Germany

    Martina U. Muckenthaler & Sandro Altamura

  3. Department of Pediatric Hematology and Oncology, Medical University, Hannover, Germany

    Hansjörg Schmid

  4. Department of Hematology and Oncology, University Children’s Hospital, Munich, Germany

    Ulrike Graubner

  5. Internal Medicine/Hematology and Oncology, Medical Office Verpoort/Wierecky/Zeller, Hamburg, Germany

    Wolfgang Zeller

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  1. Kai Lehmberg
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Correspondence to Kai Lehmberg.

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Kai Lehmberg and Regine Grosse equally contributed to this work.

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Lehmberg, K., Grosse, R., Muckenthaler, M.U. et al. Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients. Ann Hematol 92, 387–394 (2013). https://doi.org/10.1007/s00277-012-1618-8

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