Disease relevance of Hemochromatosis

• We measured iron, TIBC, and TRF concentrations in 94 control subjects, 59 patients with alcoholic liver disease (ALD), and 20 with proven genetic hemochromatosis (GH) [1].
• Genetic hemochromatosis (GH) is an iron overload disorder mainly due to the C282Y mutation of the HFE gene [2].
• RESULTS: Heavy alcohol intake (>60 g of ethanol per day for at least 1 decade) was found in 33.1% of cases, hepatitis B virus (HBV) infection in 9.4%, HCV in 19.8%, hemochromatosis in 1.3%, alcohol and HBV in 12.0%, alcohol and HCV in 16.1%, HBV and HCV in 3.1%, and no factor in 5.2% [3].
• As observed in HFE hemochromatosis, the beta-thalassemia trait seems to aggravate the clinical picture of patients lacking TFR2, favoring higher rates of iron accumulation probably by activation of the erythroid iron regulator [4].
• Patients with chronic liver disease usually exhibit low plasma levels of testosterone with loss of libido and potency; this is also valid in male patients suffering from idiopathic hemochromatosis (IHC), in whom nowadays the diagnosis is made at an earlier age [5].

High impact information on Hemochromatosis

• CONCLUSIONS: Hereditary hemochromatosis can occur in adults who do not have pathogenic mutations in the hemochromatosis gene [6].
• This points to different kinetics of intestinal iron uptake between iron deficiency and HFE hemochromatosis and also indicates that duodenal iron accumulation in HFE and non-HFE hemochromatosis is pathophysiologically different [7].
• Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to severe iron loading in the 2d to 3d decade of life [8].
• Hepcidin is decreased in TFR2 hemochromatosis [9].
• RNA-bandshift assays showed a significant increase in IRP activity in monocytes from 16 patients with untreated GH compared with 28 control subjects (1.5-fold) and five patients with secondary hemochromatosis (SH) with similar iron burden (fourfold) [10].

Chemical compound and disease context of Hemochromatosis

• The effect on urinary iron excretion (UIE) of vitamin C administered orally 2 h after the start of an 8-hour desferrioxamine (DF) i.v. infusion was studied in 12 patients with untreated idiopathic hemochromatosis (IH) [11].
• Pancreatic islet cells were examined ultrastructurally in rats after repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA) to produce a model of bronze diabetes [12].

Biological context of Hemochromatosis

• BACKGROUND & AIMS: Hereditary hemochromatosis is a common disorder of iron homeostasis characterized by increased dietary iron absorption and progressive iron accumulation, mainly in the liver [13].
• Intestinal absorption of iron in HFE-1 hemochromatosis: local or systemic process [14]?
• RESULTS: Data were available for 279 siblings known to be HH homozygotes (HHs), and 1,265 other siblings of HH patients, who are predominantly hemochromatosis heterozygotes (HHhet) [15].
• In the present article, the frequency, penetrance and pathophysiology of HFE-1 hemochromatosis as well as various clinical presentations resulting from different mutations affecting different proteins involved in iron metabolism are described [16].

Gene context of Hemochromatosis

• Patients with C282Y HFE hemochromatosis also have inappropriately low hepcidin levels for the degree of iron loading [9].
• In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion [17].
• Unsaturated iron binding capacity and transferrin saturation are equally reliable in detection of HFE hemochromatosis [18].
• Juvenile hemochromatosis (JH) is an autosomal recessive condition that leads to significant morbidity due to early onset systemic iron overload [19].
• Ten putative positive clones were identified, one of which was found to be a partial cDNA of the hemochromatosis candidate gene V (HCG V) whose function was previously unknown [20].

Analytical, diagnostic and therapeutic context of Hemochromatosis

• LightCycler PCR assay for simultaneous detection of the H63D and S65C mutations in the HFE hemochromatosis gene based on opposite melting temperature shifts [21].

References