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Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity

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Journal of Inherited Metabolic Disease

Abstract

Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. In addition to photosensitivity, patients frequently exhibit low serum iron and a microcytic hypochromic anemia. The aims of this study were to (1) search for factors related to PPIX concentration in EPP, and (2) characterize anemia in EPP, i.e., whether it is the result of an absolute iron deficiency or the anemia of chronic disease (ACD). Blood samples from 67 EPP patients (51 Italian and 16 Swiss) and 21 healthy volunteers were analyzed. EPP patients had lower ferritin (p = 0.021) and hepcidin (p = 0.031) concentrations and higher zinc–protoporphyrin (p < 0.0001) and soluble-transferrin-receptor (p = 0.0007) concentrations compared with controls. This indicated that anemia in EPP resulted from an absolute iron deficiency. Among EPP patients, PPIX concentrations correlated with both growth differentiation factor (GDF) 15 (p = 0.012) and male gender (p = 0.015). Among a subgroup of patients who were iron replete, hemoglobin levels were normal, which suggested that iron but not ferrochelatase is the limiting factor in heme synthesis of individuals with EPP.

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Acknowledgements

This work was supported by the Foundation of Scientific Research at Triemli Hospital.

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Authors and Affiliations

  1. Institute for Laboratory Medicine, Stadtspital Triemli, Zürich, Switzerland

    Jasmin Barman-Aksoezen, Xiaoye Schneider-Yin & Elisabeth I. Minder

  2. Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy

    Domenico Girelli & Natascia Campostrini

  3. Porphyria Centre San Gallicano Dermatological Institute IRCCS, Rome, Italy

    Caterina Aurizi, Luca Barbieri & Gianfranco Biolcati

Authors
  1. Jasmin Barman-Aksoezen
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  2. Domenico Girelli
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  3. Caterina Aurizi
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  4. Xiaoye Schneider-Yin
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Correspondence to Elisabeth I. Minder.

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Communicated by: Robert J Desnick

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Barman-Aksoezen, J., Girelli, D., Aurizi, C. et al. Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity. J Inherit Metab Dis 40, 433–441 (2017). https://doi.org/10.1007/s10545-017-0017-7

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  • DOI: https://doi.org/10.1007/s10545-017-0017-7

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