SEARCH · PubMed Health

Results for “HEMOCHROMATOSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed1996

Hemochromatosis: association of severity of iron overload with genetic markers.

We postulated that the severity of iron overload in homozygous hemochromatosis probands is related to the expression of HLA-A3 or D6S105 allele 8. Therefore, we used these markers to characterize Alabama hemochromatosis probands and normal control subjects. We then quantified the blood removed by phlebotomy to exhaust body iron stores and maintain normal serum ferritin concentrations in our hemochromatosis probands. Induction and maintenance phlebotomy requirements were significantly greater in presumed HLA-A3 homozygotes or in D6S105 allele 8 homozygotes than in homozygous probands lacking these markers. Intermediate values were observed in probands who were HLA-A3 or allele 8 heterozygotes, respectively. We also analyzed data from males and females separately. Among subjects of the same sex, the induction and maintenance phlebotomy requirements in subjects presumed to be HLA-A3 homozygotes or in allele 8 homozygotes were greater than those of other groups. Our results support the hypothesis that the severity of iron overload in hemochromatosis is determined predominantly by genetic factors, and provide evidence that two or more mutations for hemochromatosis exist. However, the design of our study does not permit a distinction to be made between allelic and locus heterogeneity for the hemochromatosis gene(s).

Alleles↗

PubMed2000

Nramp2 analysis in hemochromatosis probands.

The mechanism that leads to iron overload in hereditary hemochromatosis is not yet fully understood and genes other than HFE may be involved. Nramp2 is an intestinal iron transporter, upregulated by dietary iron deficiency, which also colocalizes with transferrin in recycling endosomes. The purpose of the present study was to analyze the coding region of the Nramp2 gene in 14 hemochromatosis probands which did not carry any HFE mutations on both chromosomes. We confirmed the existence of a polymorphism (1254 T --> C), which presumably is not associated with hereditary hemochromatosis, but we did not find any mutation. On the other hand, we identified 17 splice variants of the Nramp2 mRNA. Eight corresponded to activation of cryptic splicing sequences between exons 3 and 4. They were observed in a majority of hemochromatosis probands and control subjects. This indicates the existence of an important splicing instability in this region. At this stage, the biological significance of these variants is unclear. Our study did not find evidence for the involvement of the Nramp2 gene in hereditary hemochromatosis. The remaining question is whether hemochromatosis probands in our study have iron overload because of environmental factors or due to mutation in gene(s) other than HFE and Nramp2.

Alternative Splicing↗

PubMed1989

Biliary excretion of iron and ferritin in idiopathic hemochromatosis.

The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

Adult↗

PubMed1989

Immunohistochemical evidence for a lack of ferritin in duodenal absorptive epithelial cells in idiopathic hemochromatosis.

Patients with idiopathic hemochromatosis exhibit an unexplained increase in intestinal iron absorption. The aim of this work was to study immunohistochemical H- and L-ferritin distribution in duodenal mucosal cells of patients with idiopathic hemochromatosis, and of subjects with various degrees of iron loading. Biopsy sections of gastrointestinal mucosa from 24 patients with idiopathic hemochromatosis, 10 patients with secondary iron overload, 6 normal subjects, and 13 iron-deficient subjects were analyzed with monoclonal antibodies for the presence of immunohistochemical H and L ferritin types, and with Perls' stain for hemosiderin. Ferritin content of duodenal homogenates was evaluated in 5 cases. The absorptive duodenal cells were found to contain ferritin, mostly of the L type, in apical granules; these ferritin granules were present in all normal, iron-deficient, and iron-over-loaded subjects, but were absent in 21 (87%) of the patients with established idiopathic hemochromatosis. In cells other than those of the duodenal epithelium, such as lamina propria or antral mucosa, ferritin and hemosiderin contents were related to iron loading and no difference was evident between primary and secondary iron overload. These findings indicate that (a) idiopathic hemochromatosis is associated with an altered ferritin expression in the duodenal absorptive epithelial cells, (b) this alteration cannot be detected by analysis of duodenal homogenates, (c) idiopathic hemochromatosis does not affect ferritin accumulation in the other cell types analyzed, and (d) ferritin in absorptive duodenal cells may have a regulatory role in iron absorption.

Antibodies, Monoclonal↗

PubMed1997

Prevalence of hemochromatosis among first-time and repeat blood donors in Norway.

BACKGROUND/AIMS: The observed prevalence of hemochromatosis has ranged considerably from 0.05 to 0.37% in studies requiring liver biopsy. We aimed to study the prevalence of genetic hemochromatosis among Norwegian blood donors. METHODS: We studied 10,552 healthy blood donors (5312 women and 5240 men) using serum ferritin as a screening parameter. If serum ferritin concentration was > or = 100 micrograms/l in women and > or = 200 micrograms/l in men, serum iron and transferrin (measured as total iron binding capacity = TIBC) were measured. Blood donors who repeatedly had a transferrin saturation above 40% and a ferritin concentration above these limits were referred to a hepatologist (H.B.). RESULTS: Serum ferritin was > or = 100 micrograms/l in 94/5312 (1.8%) women and > or = 200 microliters in 79/5240 (1.5%) men. Of these, 37 persons had a serum ferritin concentration above 100 micrograms/l (females) or above 200 micrograms/l (males) and a transferrin saturation above 40%. Nineteen of them (13 men and 6 women, median age 36 years, range 28-68) were identified as having hemochromatosis on the basis of increased hepatic iron index. Serum ferritin ranged from 111 to 1980 micrograms/l (median 357 micrograms/l and transferrin saturation from 50 to 100% (median 92%), hepatic iron from 48 to 471 mumol/g dry weight (median 118 mumol/g) and hepatic iron index from 1.5 to 12.1 (median 3.0). One person had cirrhosis and none had diabetes. The prevalence of hemochromatosis was significantly higher among first-time blood donors (12 out of 3500 [3.4/1000]) compared with repeat donors (7 out of 7052 [1/1000]), p < 0.005. CONCLUSIONS: The observed prevalence of hemochromatosis in Norwegian first-time blood donors of 0.34% is comparable to recently observed prevalences in other studies. However, the use of serum ferritin as a first-step screening tool may have failed to detect hemochromatosis in the early stage where iron overload has not yet occurred.

Adolescent↗

PubMed2000

Disease-related conditions in relatives of patients with hemochromatosis.

BACKGROUND: Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations in the HLA-linked HFE gene. Although screening has been proposed, the proportion of homozygotes with conditions related to hemochromatosis is uncertain. METHODS: We studied the prevalence of disease-related conditions among relatives of probands with hemochromatosis. We identified probands who presented to a clinic with signs or symptoms of hemochromatosis or who had elevated transferrin-saturation values. We identified homozygous relatives, mainly siblings, on the basis of HLA identity with the proband and by HFE genotyping. Disease-related conditions were cirrhosis, hepatic fibrosis, elevated amino-transferase values, and hemochromatotic arthropathy. RESULTS: We identified 214 homozygous relatives of 291 homozygous probands. Of the 113 men in this group (mean age, 41 years), 96 (85 percent) had iron overload, and 43 (38 percent) had at least one disease-related condition. Of the 52 men over 40 years of age, 27 (52 percent) had at least one disease-related condition. Of the 101 female homozygous relatives (mean age, 44 years), 69 (68 percent) had iron overload, and 10 (10 percent) had at least one disease-related condition. Of the 43 women over 50 years of age, 7 (16 percent) had at least one disease-related condition. If the proband had a disease-related condition, relatives who were men were more likely to have morbidity than if the proband had no disease-related condition. CONCLUSIONS: A substantial number of homozygous relatives of patients with hemochromatosis--more commonly men than women--have conditions related to hemochromatosis that have yet to be detected clinically.

Adult↗

PubMed1997

A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of hemochromatosis.

The aim of this study was to describe the histologic pattern of iron distribution in end-stage cirrhosis due to various causes and to test the reliability of the hepatic iron index (equal to hepatic iron concentration divided by age) in excluding or confirming associated hemochromatosis in such a condition. Large slices of the resected livers of 30 patients transplanted for alcoholic and/or viral end-stage cirrhosis were assessed histologically for iron distribution and biochemically for hepatic iron concentration in the least and the most iron-overloaded nodules of each case. HLA-A3 was used as the marker for the hemochromatosis gene in the population studied. Intranodular parenchymal siderosis was found in 23 cases (12 spotty, 11 diffuse) with diffuse intrabiliary iron deposits apparent in only two cases. Although in 14 patients the hepatic iron index was significantly high (> 1.9) so as to suggest hemochromatosis, these cases did not correspond to homozygous hemochromatosis with respect to the prevalence of HLA-A3 antigen. End-stage cirrhosis arising from different causes is frequently complicated by parenchymal siderosis that may mimic hemochromatosis, including a hepatic iron index greater than 1.9. The diagnosis of hemochromatosis in patients with end-stage cirrhosis, even those with a hepatic iron index greater than 1.9, should rely mainly on clinical and histologic data.

Adult↗

PubMed1996

Correlation of liver density by magnetic resonance imaging and hepatic iron levels. A noninvasive means to exclude homozygous hemochromatosis.

The diagnosis of hemochromatosis requires liver biopsy and the quantification of hepatic iron. Magnetic resonance imaging (MRI) of the liver shows a characteristic decrease in tissue signal intensity in iron overload states, but its role in the diagnosis of hemochromatosis has not been fully delineated. Forty-three patients (31 men and 12 women) were referred for the evaluation of hemochromatosis based upon a fasting transferrin saturation > 55% and/or a serum ferritin > 400 ng/ml in males or > 300 ng/ml in females. Each patient prospectively underwent MRI of the liver prior to percutaneous liver biopsy and quantitative hepatic iron determination. Homozygous hemochromatosis was diagnosed in 10 patients based upon an hepatic iron/age index > or = 2. MRI was performed with a 1.5 Tesla system using standard spin-echo sequences (T1; TR = 300-500 ms, TE = 13-17 ms, PD; TR = 2,000-2,600 ms, TE = 30 ms). Signal intensity values were blindly determined for regions of interest in liver and skeletal muscle at T1 and proton density. Ratios of liver to muscle (LM) for T1 and proton density (PD) calculated from these values showed a significant correlation with quantitative iron by multiple regression analysis. The LMPD ratio provided the best correlation with hepatic iron (r = -0.6946; p < 0.001). Linear regression analysis also provides an equation that can be used to predict hepatic iron based upon the LMPD ratio; micrograms/g of hepatic iron = (-5,174 x LMPD) + 9,932. All patients with LMPD ratios of > 0.5 had hepatic iron/age indices of < 2.0, thereby excluding homozygous hemochromatosis. These results suggest that LMPD ratios derived from MRI of the liver can accurately predict hepatic iron content. These ratios can be clinically useful in the evaluation of hemochromatosis among patients who either refuse or have contraindications to liver biopsy.

Adult↗

PubMed2002

Unsaturated iron binding capacity and transferrin saturation are equally reliable in detection of HFE hemochromatosis.

OBJECTIVE: Unsaturated iron binding capacity (UIBC) has been proposed as an inexpensive alternative to transferrin saturation for detection of hereditary hemochromatosis. The aim of this study was to compare, in a hospital referral clinic, the reliability of transferrin saturation and UIBC for detection of subjects who have inherited HFE (HLA-asociated iron overload) genotypes predisposing to iron overload. METHODS: Serum transferrin saturation, UIBC, and ferritin were tested in 110 consecutive subjects. Optimum thresholds were determined from receiver operating characteristic curves. RESULTS: Of 110 subjects, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). In genetically predisposed subjects with biochemical expression, the optimum threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and specificity 0.95. For UIBC, the optimum threshold was 143 microg/dL (25.6 micromol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients referred with a family history or clinical suspicion of hemochromatosis, transferrin saturation and UIBC were highly reliable predictors of genotype. In patients referred for investigation of abnormal liver enzymes without a known family history of hemochromatosis, a normal transferrin saturation or normal UIBC was highly reliable in excluding hemochromatosis. CONCLUSIONS: Transferrin saturation and UIBC have equal reliability in ability to predict hemochromatosis. UIBC should be considered as an alternative to transferrin saturation in detection of hemochromatosis.

Bayes Theorem↗

PubMed2006

Surgery for hepatocellular carcinoma arising in hereditary hemochromatosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a well-known complication of hereditary hemochromatosis. The benefit of surgical therapy in this clinical entity is not well documented. The purpose of this study was to evaluate the outcome of such patients both in our own experience as well as in the published literature. METHODS: 320 patients with a diagnosis of HCC were evaluated at our institution to undergo either surgical resection (n = 262) or liver transplantation (n = 58) during the 4- year period from January 2001 to December 2004. We identified 5 patients with HCC arising in the setting of hemochromatosis. A literature search was performed to estimate resectability rates as well as outcomes after liver transplantation for HCC arising in hemochromatosis. RESULTS: HCC was multifocal in 4 instances and solitary in 1 case. The liver was cirrhotic in all but 1 case. Three patients underwent an exploratory laparotomy, 1 an exploratory laparoscopy, and 1 underwent transplantation. HCC was unresectable in all cases. The patient with a solitary tumor and cirrhosis underwent 5 sessions of transarterial chemoembolization and is alive 37 months after surgical exploration. The 3 patients with multifocal tumors who underwent exploratory laparotomies died within 6 months after the intervention. The fifth patient who underwent a deceased donor split liver transplantation for multifocal tumor is alive without recurrence 3 years after transplantation. These results are similar to those in the literature that concur with the low resectability rate and the favorable outcome after liver transplantation. CONCLUSION: Resectability rates of HCCs arising in hemochromatosis are extremely low, given that tumors are usually multifocal and the livers cirrhotic in the majority of the instances. Early detection of hemochromatosis as well as intensive tumor screening of cirrhotic patients with hemochromatosis could possibly optimize the role of surgery or accelerate the decision to proceed with liver transplantation.

Aged↗

PubMed2006

Current approaches to the management of hemochromatosis.

The term hemochromatosis encompasses at least four types of genetic iron overload conditions, most of them recently distinguished from one another as a result of the identification of a series of genes related to iron metabolism. At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. Major advances in the management of hemochromatosis influence the diagnostic approach to the disease, with the development of an overall non invasive strategy, mainly based on clinical, biological (iron parameters and genetic testing), and imaging (especially magnetic resonance imaging) data. Therapeutic management remains, on the curative side, dominated by phlebotomy (venesection), practical aspects of which have been recently revisited by the Guidelines Department of the French "Haute Autorité de Santé." However, innovative treatment approaches, based on the improved pathophysiological understanding of these diseases and the progress in iron chelation therapy, are emerging. Preventive therapy, focused on family screening, remains a key part of the management of hemochromatosis.

Antimicrobial Cationic Peptides↗

PubMed2002

Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis.

Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE-related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in the ferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

Adult↗

PubMed2006

Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages.

Iron (Fe) acquisition is essential for the growth of intracellular Mycobacterium tuberculosis (M.tb). How this occurs is poorly understood. Hereditary hemochromatosis is an inherited disease in which most cells become overloaded with Fe. However, hereditary hemochromatosis macrophages have lower than normal levels of intracellular Fe. This suggests M.tb growth should be slower in those cells if macrophage intracellular Fe is used by M.tb. Therefore, we compared trafficking and acquisition of transferrin (Tf)- and lactoferrin (Lf)-chelated Fe by M.tb within the phagosome of monocyte-derived macrophages (MDM) from healthy controls and subjects with hereditary hemochromatosis. M.tb in both sets of macrophages acquired more Fe from Lf than Tf. Fe acquisition by M.tb within hereditary hemochromatosis macrophages was decreased by 84% from Tf and 92% from Lf relative to that in healthy control macrophages. There was no difference in Fe acquired from Tf and Lf by the two macrophage phenotypes. Both acquired 3 times more Fe from Lf than Tf. M.tb infection and incubation with interferon gamma (IFN-gamma) reduced macrophage Fe acquisition by 20% and 50%, respectively. Both Tf and Lf colocalized with M.tb phagosomes to a similar extent, independent of macrophage phenotype. M.tb growth was 50% less in hereditary hemochromatosis macrophages. M.tb growing within macrophages from subjects with hereditary hemochromatosis acquire less Fe compared with healthy controls. This is associated with reduced growth of M.tb. These data support a role for macrophage intracellular Fe as a source for M.tb growth.

Case-Control Studies↗

PubMed1989

Hypogonadism and sexual dysfunction in hemochromatosis: the effects of cirrhosis and diabetes.

The contribution of diabetes and cirrhosis to sexual dysfunction and hypogonadism was evaluated by two-way analysis of variance in a group of 30 men with idiopathic hemochromatosis. The prevalence of severe sexual dysfunction was significantly higher in men with hemochromatosis than in a control group matched for prevalence of diabetes and age (P less than 0.001). In both controls and hemochromatosis patients the presence of diabetes was significantly associated with sexual dysfunction (P less than 0.005), but the more severe symptoms in the hemochromatosis patients were related to the additive effects of hypoandrogenism (P less than 0.01). Sexual dysfunction was a common early complaint in hemochromatosis patients, but these symptoms were frequently overlooked, leading to diagnostic delay. Mean testicular volume was a useful measure of gonadal status, being significantly correlated with indices of serum free testosterone (rs = 0.83; P less than 0.01) and LH (rs = 0.71; P less than 0.001). The presence of cirrhosis did not contribute significantly to symptomatology, but had an effect independent of and additive to hypogonadotropic hypogonadism in reducing serum free testosterone (P less than 0.02) and estradiol (P less than 0.002), an effect apparently mediated through central rather than testicular mechanisms. Hypoandrogenism was associated with an increase in serum sex hormone-binding globulin (SHBG) concentrations (P less than 0.005), but cirrhosis also had an independent effect in raising SHBG (P less than 0.005), which could not be accounted for by changes in circulating sex hormone concentrations. Thus, the evaluation of sexual dysfunction or hypogonadism in men with hemochromatosis requires consideration of the effects of both diabetes and cirrhosis. Because of the greater variance in SHBG some estimate of free testosterone rather than total testosterone is preferable.

Adult↗

PubMed1998

Strategies to increase detection of hemochromatosis.

As part of the Iron Overload, Public Health and Genetics conference, sponsored by the Centers for Disease Control and Prevention in March 1997, a working group was convened to consider strategies to increase early case detection of hemochromatosis. This group emphasized that the primary public health goal should be to diagnose hemochromatosis before symptoms appear. To reach this goal, education and action need to be targeted to physicians and other health care workers, laboratorians, administrators, payers, and the public. Strategies to disseminate updated information and increase early case detection were prioritized according to expected effectiveness. Strategies targeting physicians are 1) to identify national and local physician-leaders and 2) to educate physicians about hemochromatosis in basic, graduate specialty, and continuing medical education. Strategies aimed at the health system are 1) to encourage laboratories to provide the transferrin saturation test as part of routine laboratory panels and 2) to work with policymakers and payers to allow reimbursement for case detection. Finally, public education is recommended to increase lay support for the early diagnosis of hemochromatosis. Attempts to educate the public should be aimed first at persons who receive diagnoses of hemochromatosis in order to ensure that they are properly treated and then at asymptomatic persons who could be screened as part of health appraisals. Although identifying physician-leaders and educating physicians are the highest priorities, physicians should not be targeted at the exclusion of payers and the public. Simultaneous efforts to reach all groups in appropriate ways should be initiated to provide the interest and infrastructure necessary to decrease morbidity and mortality from hemochromatosis.

Clinical Laboratory Techniques↗

PubMed1999

HFE genotype in patients with hemochromatosis and other liver diseases.

BACKGROUND: Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified. OBJECTIVE: To determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENTS: 66 patients with hereditary hemochromatosis and 132 referred patients with other liver diseases. MEASUREMENTS: At initial diagnosis, fasting transferrin saturation, ferritin level, routine chemistry panel, and complete blood count were determined. Percutaneous liver biopsy was done on all patients for histologic analysis and measurement of hepatic iron concentration and hepatic iron index. HFE genotyping for the C282Y and H63D mutations was done on all patients by using genomic DNA samples. RESULTS: Of the 66 patients with hemochromatosis diagnosed on the basis of serum iron studies and liver biopsy findings, 60 (91%) were C282Y homozygotes, 2 (3%) were compound heterozygotes, 1 (1.5%) was a C282Y heterozygote, 2 (3%) were H63D heterozygotes, and 1 (1.5%) was negative for both mutations. Of the 132 patients with liver disease, 6 (5%) were C282Y homozygotes, 8 (6%) were compound heterozygotes, 6 (5%) were C282Y heterozygotes, 5 (4%) were H63D homozygotes, 20 (15%) were H63D heterozygotes, and 87 (66%) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98%) had a transferrin saturation of at least 45%. Ten of the 66 patients (15% [95% CI, 7.5% to 26%]) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotyping. Cirrhosis or substantial hepatic fibrosis was not seen in any (0% [CI, 0% to 18%]) of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation. CONCLUSIONS: All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.

Adult↗

PubMed2004

Countries of ancestry reported by hemochromatosis probands and control subjects in central Alabama.

OBJECTIVES: We sought to evaluate the hypothesis that the relatively high HFE C282Y allele frequency in White persons in central Alabama (0.0896) is due to a predominance of persons of Irish and Scots descent, and is not attributable to Native American ancestry common in this geographic area. DESIGN: Eighty evaluable hemochromatosis probands with C282Y homozygosity and 319 White controls reported countries of ancestry of their grandparents. Frequencies of country of ancestry reports were tabulated. The reports were also converted to scores that reflect proportional countries of ancestry in individuals. Using the scores, we computed aggregate country of ancestry indices as estimates of group ancestry composition. Results were compared to those of European populations with C282Y allele frequencies >0.0800. RESULTS: The respective frequencies of "British Isles" and Scotland reports were significantly greater in hemochromatosis probands than in controls. The respective frequencies of "Europe Not British Isles," Italy, and Poland reports were significantly greater in controls. Aggregate "British Isles" and Scotland indices were significantly greater in hemochromatosis probands. The "Europe Not British Isles" index was significantly greater in controls. Approximately one-quarter of hemochromatosis probands and controls reported "Native American" ancestry; the corresponding country of ancestry index was not significantly different in probands and controls. C282Y frequencies >0.0800 were reported from England, Ireland, Scotland, Wales, Brittany, and Denmark. CONCLUSIONS: The present results indicate that hemochromatosis probands with C282Y homozygosity in central Alabama report significantly different countries of ancestry than control subjects. It is unlikely that Native American ancestry is associated with an enrichment of hemochromatosis among adult probands. British Isles ancestry, not exclusively Irish and Scots ancestries, likely accounts for the relatively high C282Y frequency in White persons in central Alabama.

Adolescent↗

PubMed1992

Decreased concentrations of tumor necrosis factor-alpha in supernatants of monocytes from homozygotes for hereditary hemochromatosis.

To determine whether release of tumor necrosis factor-alpha (TNF-alpha), a cytokine that affects iron homeostasis, may be selectively altered in hereditary hemochromatosis, we measured concentrations of TNF-alpha and interleukin-1 beta (IL-1 beta) in supernatants of cultured peripheral blood monocytes from 11 homozygotes for hereditary hemochromatosis, 11 healthy individuals, and five patients with iron-loading anemia. The gene for hereditary hemochromatosis is tightly linked to the HLA locus on chromosome 6, but its exact site and product are not known. The gene for TNF-alpha also is located within the HLA region. Monocytes were incubated from 4 to 36 hours in medium alone or with added lipopolysaccharide. Mean concentrations of immunoreactive TNF-alpha in supernatants were significantly lower for subjects with hereditary hemochromatosis as compared to healthy controls (P less than .037) and patients with iron-loading anemia (P less than .005); differences between homozygotes for hemochromatosis and healthy controls were up to 4.5-fold at 4 hours (P = .008), 1.9-fold at 12 hours (P = .036), and 7.0-fold at 36 hours (P = .001). Importantly, concentrations of IL-1 beta in supernatants were not significantly different among the three groups. We conclude that release of TNF-alpha by monocytes may be selectively impaired in hereditary hemochromatosis. Deficient activity of TNF-alpha may contribute to the disordered iron metabolism of this disease.

Adult↗