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

J Gastroenterol (2010) 45:11631171 DOI 10.1007/s00535-010-0259-8

ORIGINAL ARTICLELIVER, PANCREAS, AND BILIARY TRACT

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

Yoshibumi Kaneko Hiroaki Miyajima Alberto Piperno Naohisa Tomosugi Hisao Hayashi

Natsuko Morotomi Ken-ichi Tsuchida Takaaki Ikeda Akihisa Ishikawa Yusuke Ota

Shinya Wakusawa Kentaro Yoshioka Satoshi Kono Sara Pelucchi Ai Hattori Yasuaki Tatsumi

Toshihide Okada Masakazu Yamagishi

Received: 7 December 2009 / Accepted: 9 May 2010 / Published online: 9 June 2010 Springer 2010

AbstractBackground 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 chromatographytandem 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 remaining7 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

Y. Kaneko (&) T. Okada M. Yamagishi

Department of Internal Medicine,Graduate School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, Japan e-mail: [email protected]

H. Miyajima S. Kono

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

A. Piperno S. Pelucchi

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

N. TomosugiDivision of Nephrology, Department of Internal Medicine, Kanazawa Medical University, Kanazawa, Japan

H. Hayashi A. Hattori Y. Tatsumi

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

N. MorotomiDepartment of Internal Medicine,Kitakyushu Municipal Moji Hospital, Kitakyushu, Japan

K. TsuchidaDepartment of Internal Medicine,Manda Memorial Hospital, Sapporo, Japan

T. IkedaDepartment of Internal Medicine,Yokosuka Kyousai Hospital, Yokosuka, Japan

A. IshikawaDepartment of Gastroenterology, Hitachi General Hospital, Hitachi, Japan

Y....