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

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. (231 words)

Patients with Chronic Hepatitis C May be More Sensitive to Iron Hepatotoxicity than Patients with HFE-Hemochromatosis

“…The current observations of circulating hepcidin 25 confirmed the findings previously observed in urine from patients with HFE-hemochromatosis (12). Low levels of serum hepcidin 25 were also found in Japanese patients with non-HFE hemochromatosis (18). In CHC patients, the mechanism of hepatic iron accumulation appears to be more complex and is still not completely understood.…”

Hepcidin in the diagnosis of iron disorders

“…56 Some data support using hepcidin measurement as a guide for the follow-up genetic testing of IO patients, particularly in populations in whom classical type 1 HFErelated HH is rare. 57 Furthermore, during treatment of type 1 HH, monitoring hepcidin to prevent its complete suppression may curb iron hyperabsorption in the maintenance phase, possibly decreasing the need for phlebotomies. In iron-loading anemias, hepcidin measurement may also be valuable for identifying the most severely affected patients, helping to predict the development of IO and guiding the therapy.…”

A Novel Phenotype of a Hereditary Hemochromatosis Type 4 with Ferroportin-1 Mutation, Presenting with Juvenile Cataracts

“…Although not confirmed by liver biopsy, the present case was considered to be H-type because TSAT was found to be elevated. To the best of our knowledge, only three cases of type 4 HH (one M-type and two H-type) have been reported in Japan (3)(4)(5). This is the first Japanese case of p.His507Arg in SLC40A1.…”