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Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes.

Methods

We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography–tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis.

Results

One patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes.

Conclusion

Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.

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Authors and Affiliations

  1. Department of Internal Medicine, Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, Japan

    Yoshibumi Kaneko, Toshihide Okada & Masakazu Yamagishi

  2. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Hiroaki Miyajima & Satoshi Kono

  3. Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy

    Alberto Piperno & Sara Pelucchi

  4. Division of Nephrology, Department of Internal Medicine, Kanazawa Medical University, Kanazawa, Japan

    Naohisa Tomosugi

  5. Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan

    Hisao Hayashi, Ai Hattori & Yasuaki Tatsumi

  6. Department of Internal Medicine, Kitakyushu Municipal Moji Hospital, Kitakyushu, Japan

    Natsuko Morotomi

  7. Department of Internal Medicine, Manda Memorial Hospital, Sapporo, Japan

    Ken-ichi Tsuchida

  8. Department of Internal Medicine, Yokosuka Kyousai Hospital, Yokosuka, Japan

    Takaaki Ikeda

  9. Department of Gastroenterology, Hitachi General Hospital, Hitachi, Japan

    Akihisa Ishikawa

  10. Department of Rheumatology, Minami-Okayama Medical Center, Hayashima, Japan

    Yusuke Ota

  11. Medical Technology of Health Sciences, Nagoya University School of Medicine, Nagoya, Japan

    Shinya Wakusawa

  12. Department of Gastroenterology, Fujita Health University Hospital, Toyoake, Japan

    Kentaro Yoshioka

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  1. Yoshibumi Kaneko
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  2. Hiroaki Miyajima
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  13. Satoshi Kono
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  14. Sara Pelucchi
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  15. Ai Hattori
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  18. Masakazu Yamagishi
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Correspondence to Yoshibumi Kaneko.

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Kaneko, Y., Miyajima, H., Piperno, A. et al. Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders. J Gastroenterol 45, 1163–1171 (2010). https://doi.org/10.1007/s00535-010-0259-8

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  • DOI: https://doi.org/10.1007/s00535-010-0259-8

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