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


CONCLUSIONS
Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.
Department of Internal Medicine, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan. mdyoshi@arion.ocn.ne.jp
Yoshibumi
Y
Kaneko
Hiroaki
H
Miyajima
Alberto
A
Piperno
Naohisa
N
Tomosugi
Hisao
H
Hayashi
Natsuko
N
Morotomi
Ken-ichi
K
Tsuchida
Takaaki
T
Ikeda
Akihisa
A
Ishikawa
Yusuke
Y
Ota
Shinya
S
Wakusawa
Kentaro
K
Yoshioka
Satoshi
S
Kono
Sara
S
Pelucchi
Ai
A
Hattori
Yasuaki
Y
Tatsumi
Toshihide
T
Okada
Masakazu
M
Yamagishi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers; D002570:Ceruloplasmin / Q000172:deficiency / Q000235:genetics; D002853:Chromatography, Liquid / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics; D064451:Hepcidins; D006801:Humans; D019189:Iron Metabolism Disorders / Q000175:diagnosis / Q000235:genetics; D019190:Iron Overload / Q000175:diagnosis* / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics; D053719:Tandem Mass Spectrometry / Q000379:methods
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D064451:Hepcidins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; C545475:hepcidin 25, human; D002570:Ceruloplasmin