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At least 667 records · Page 37Linked to original sources
PubMed1995

Duodenal ferritin synthesis in genetic hemochromatosis.

BACKGROUND/AIMS: The molecular defect of genetic hemochromatosis (GH) is unknown. It is believed that low expression of duodenal ferritin in GH is caused by tissue or cell specific defect of ferritin synthesis. Our study was designed to ascertain whether the control of duodenal ferritin synthesis in GH was defective. METHODS: Expression at the single cell level of H and L ferritin messenger RNAs and protein and activity of the iron regulatory factor, which controls the translation of ferritin messenger RNA, were assessed in 43 duodenal biopsy specimens from individuals with GH, secondary hemochromatosis (SH), anemia, or normal iron balance. RESULTS: Signal for ferritin H and L subunit messenger RNAs was detected in both absorptive and nonabsorptive cells by in situ hybridization, but in 10 of 14 patients with untreated GH, the signal was lower than in patients with SH or normal subjects. However, immunostaining for ferritin protein documented a diffuse/cytoplasmic pattern, whereas a supranuclear/granular staining was found in normal subjects or patients with SH. The spontaneous activity of duodenal iron regulatory factor was consistently higher in patients with GH than in normal subjects or subjects with anemia or SH. CONCLUSIONS: In patients with GH, ferritin gene transcription is preserved in both absorptive and nonabsorptive intestinal cells. Low accumulation of ferritin is not caused by a defective control of ferritin synthesis but by low expression of ferritin messenger RNA and sustained activity of iron regulatory factor.

Adolescent↗
PubMed1992

Cytomegalovirus infection, fetal liver disease, and neonatal hemochromatosis.

Neonatal hemochromatosis is an uncommon disorder, clinicopathologically defined by severe and generally fatal liver disease of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements (hemochromatotic siderosis). The agent or agents of liver disease in neonatal hemochromatosis are not known. It also is not known if intrauterine liver disease of defined infective etiology can lead to hemochromatotic siderosis. We present two patients with fetal liver disease and hemochromatotic siderosis whose cases help address these points. In the first patient rare hepatobiliary and numerous renal tubular cytomegalovirus (CMV) inclusions were found; CMV infection was confirmed by the polymerase chain reaction. Studies of the mother of the second patient 1, 5, and 9 weeks post-partum showed recent seroconversion against CMV; seroconversion against other infectious agents (toxoplasma, rubella, herpes, parvovirus B19, hepatitis A/B/C) was not present. Histologic, immunohistochemical, in situ hybridization, or polymerase chain reaction evidence of CMV infection was not present in infant tissues, even though peripartum maternal seroconversion against CMV was observed. We conclude that hemochromatotic siderosis may accompany chronic fetal liver disease of defined infective etiology (patient no. 1) and that recent maternal seroconversion against CMV in the presence of severe fetal liver disease does not necessarily mean that transplacentally acquired CMV infection caused the fetal liver disease (patient no. 2). Polymerase chain reaction documentation of infective-agent genomic sequences in fetal or infant tissues permits more accurate interpretation of maternal serologic data.

Adolescent↗
PubMed1990

Liver cell damage and lysosomal iron storage in patients with idiopathic hemochromatosis. A light and electron microscopic study.

Eleven patients with idiopathic hemochromatosis were subjected to percutaneous liver biopsy, and seven were rebiopsied after repeated phlebotomies. The liver tissue was examined by light and electron microscopy. Ultrastructural morphometry was also performed and iron content was determined. Initially, all biopsies displayed large iron-laden lysosomes in the hepatocytes. Lysosomal volume density was increased and correlated well with liver iron content (r = 0.84, p less than 0.005). Neither mitochondria nor the endoplasmic reticulum showed any ultrastructural changes, except in the necrotic cells of biopsies with the highest liver iron content. In these cases, iron-laden lysosomes were also encountered in the Kupffer cells. Following treatment, liver iron content and lysosomal volume density were normalized. More specifically, iron content was 14.1 +/- 2.1 micrograms Fe/mg protein before and 1.3 +/- 0.3 micrograms Fe/mg protein after treatment (p less than 0.001). Lysosomal volume density was 6.1 +/- 0.8% before and 1.8 +/- 0.2% after treatment (p less than 0.001). Hence, in the precirrhotic stage of idiopathic hemochromatosis, the first evident ultrastructural changes are in the lysosomal compartment. These changes correlate well with the iron overload, also in advanced stages of the disease, and are reversed after iron removal.

Adult↗
PubMed1992

Magnetic resonance imaging and assessment of liver iron content in genetic hemochromatosis.

Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences.

Adipose Tissue↗
PubMed1994

Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis.

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF-1, was established from a hepatocellular carcinoma of a 67-yr-old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI-1640 tissue-culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, alpha 2-macroglobulin, fibronectin and alpha-fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF-1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload.

Aged↗
PubMed1990

Heterozygous hemochromatosis as a risk factor for premature myocardial infarction.

Previous studies suggest that risk of premature myocardial infarction is increased by a heritable factor not associated with the conventional risk factors. Among the 5-7% of persons in the general population at high risk, the men are at greater risk than the women. It is proposed that heterozygosity for hemochromatosis increases the susceptibility of the carrier to premature myocardial infarction. This hypothesis explains much of the behavior of the unknown heritable factor, including its independence from the conventional risk factors and its apparent selectivity for men under age 50. Heterozygous hemochromatosis occurs frequently enough to account for the observed number of high risk families. Studies for verification of the hypothesis are proposed.

Female↗
PubMed1989

Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases.

Clinical and pathologic features of cardiac hemochromatosis diagnosed by endomyocardial biopsy in six men, aged 32 to 75 years (mean 52), are described. Echocardiography demonstrated left ventricular enlargement and marked global systolic dysfunction in five. Cardiac catheterization demonstrated normal coronary arteries, increased left ventricular end-diastolic pressure and decreased left ventricular systolic function in all five so studied. Stainable iron was present in all endomyocardial biopsy specimens from the five patients with decreased left ventricular systolic function. Histologically, iron was detected only within the sarcoplasm, and its extent varied inversely with ventricular function. Thus, cardiac hemochromatosis represents a storage rather than an infiltrative disease. These results indicate that stainable iron is consistently observed in endomyocardial biopsy specimens from patients with impaired left ventricular systolic function. Iron staining is recommended for endomyocardial biopsy specimens from patients with idiopathic cardiac dysfunction.

Adult↗
PubMed2005

A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis.

We report a new mutation, Asn185Asp, in exon 6 of the ferroportin gene (FPN1) in 15 members of three successive generations of a Canadian family of Scandinavian origin with autosomal dominant hemochromatosis. Hyperferritinemia with low transferrin saturation was noted in younger family members, seven of whom were aged 20 years or less at the time of diagnosis. In those individuals first diagnosed with hemochromatosis in later life, marked hyperferritinemia was accompanied by high transferrin saturation. In contrast to the phenotype of high ferritin with low saturation first reported for ferroportin disease, this family demonstrates a phenotype of iron indices that varies with age.

Adolescent↗
PubMed2005

The penetrance of hereditary hemochromatosis.

Since its original description as a rare disease of iron overload resulting in liver disease, diabetes mellitus, and bronzing of the skin ('bronze diabetes'), hereditary hemochromatosis has undergone several redefinitions leading to widely varying estimates of its prevalence. Over the last decade, the finding of a relatively high prevalence of the C282Y polymorphism of the HFE gene associated with hemochromatosis in Northern European populations suggested that the disease may be much more common than previously thought. However, several large population-based studies have now shown that the penetrance of the C282Y/C282Y genotype is very low, indicating that C282Y homozygosity is a necessary but not sufficient factor in causation of the disease. Studies are now focusing on other genetic and environmental factors, including alcohol, that may contribute to differential expression of C282Y homozygosity.

Age Factors↗
PubMed2005

Soluble transferrin receptor in hemochromatosis patients during phlebotomy therapy.

BACKGROUND: The monitoring of phlebotomies in hemochromatosis patients depends on iron status measured by ferritin and transferrin saturation (TS). However, in the presence of inflammation or liver injury, soluble transferrin receptor (sTfR) determination was proposed to replace ferritin for diagnosing iron deficiency (ID). The present study evaluated performances of sTfR for the prediction of iron deficiency in a large number of hemochromatosis patients under phlebotomy therapy. METHODS: We studied 52 patients undergoing therapeutic phlebotomies and obtained 2 samples from 37 patients. Biological parameters were determined before each phlebotomy began. Performances of sTfR and TS in the diagnosis of iron deficiency were compared, according to ferritin levels under 12 microg/l. RESULTS: Ferritin and TS were correlated with removed iron (r=0.473, p<0.005 and r=0.345, p<0.05, respectively) and sTfR was correlated with the decrease in hemoglobin levels induced by phlebotomies (r=-0.678, p<0.0001). Areas under Receiver Operating Characteristics (ROC) curves for sTfR and TS were not statistically different for prediction of iron deficiency and sensitivity/specificity of sTfR at 1.64 mg/l were 67/86%. CONCLUSIONS: sTfR determination could be used to predict iron depletion induced by phlebotomies when ferritin is of limited interest, to avoid the appearance of anemia.

Adult↗
PubMed2004

Hemochromatosis.

Hemochromatosis is a common genetic disease with a wide range of clinical expression: from no symptoms to cirrhosis of the liver. The discovery of the gene has led to a genetic blood test useful in the diagnosis of hemochromatosis. Treatment by phlebotomy is simple and efficient and can prevent the development of cirrhosis, leading to a normal life expectancy.

Diagnosis, Differential↗
PubMed2005

Recurrence of iron deposition in the cardiac allograft in a patient with non-HFE hemochromatosis.

We report the case of a 36-year-old woman with a diagnosis of idiopathic dilated cardiomyopathy who underwent cardiac transplantation. The results of her initial iron studies were normal, but hemochromatosis was suspected after microscopy of the explanted heart revealed iron deposition. By 6 months post-transplantation, iron deposition was detected in her surveillance endomyocardial biopsy specimens and studies then confirmed the existence of non-HFE hemochromatosis. The patient has been stable on treatment with regular phlebotomies and a low vitamin C diet.

Adult↗
PubMed2005

Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis.

BACKGROUND/AIMS: Hereditary hemochromatosis (HHC) is a disorder of iron metabolism with variable penetrance. Oxidative stress plays a central role in the progression to cirrhosis. Several enzymes involved in the production or degradation of reactive oxidants, like myeloperoxidase (MPO) and heme oxygenase (HO)-1 are influenced by promotor polymorphisms. This study assessed the impact of polymorphisms of the MPO (-463G/A) and the HO-1 promotors of Vienna (GT)n on the evolution of cirrhosis in patients with HHC. METHODS: One-hundred and fifty-eight C282Y homozygotes without cofactors for fibrosis progression (119 males; mean age: 51.0+/-13.3) were studied. All patients underwent liver biopsy. Hepatic iron content was measured by atom absorption spectrophotometry. MPO polymorphism was assessed by RFLP analysis; HO-1 microsatellite polymorphism by a laser-based semi-automated DNA sequencer. RESULTS: The MPO genotypes GG, GA, and AA were found in 102 (64.6%), 45 and 11 patients, respectively. The GG-genotype was more common in patients with cirrhosis than in those without (78.7 vs. 55.7%, P=0.003). The distribution of HO-1 genotypes was not different. Logistic regression analysis revealed MPO genotype-GG, serum ferritin, age and male sex as independent predictors for cirrhosis. CONCLUSIONS: MPO genotype GG is associated with cirrhosis in patients with hereditary hemochromatosis.

Adult↗
PubMed1998

Homogeneous multiplex genotyping of hemochromatosis mutations with fluorescent hybridization probes.

Multiplex polymerase chain reaction amplification and genotyping by fluorescent probe melting temperature (Tm) was used to simultaneously detect multiple variants in the hereditary hemochromatosis gene. Homogenous real-time analysis by fluorescent melting curves has previously been used to genotype single base mismatches; however, the current method introduces a new probe design for fluorescence resonance energy transfer and demonstrates allele multiplexing by Tm for the first time. The new probe design uses a 3'-fluorescein-labeled probe and a 5'-Cy5-labeled probe that are in fluorescence energy transfer when hybridized to the same strand internal to an unlabeled primer set. Two hundred and fifty samples were genotyped for the C282Y and H63D hemochromatosis causing mutations by fluorescent melting curves. Multiplexing was performed by including two primer sets and two probe sets in a single tube. In clinically defined groups of 117 patients and 56 controls, the C282Y mutation was found in 87% (204/234) of patient chromosomes, and the relative penetrance of the H63D mutation was 2.4% of the homozygous C282Y mutation. Results were confirmed by restriction enzyme digestion and agarose gel electrophoresis. In addition, the probe covering the H63D mutation unexpectedly identified the A193T polymorphism in some samples. This method is amenable to multiplexing and has promise for scanning unknown mutations.

Alleles↗
PubMed2001

An unusual melting curve profile in LightCycler multiplex genotyping of the hemochromatosis H63D/C282Y gene mutations.

OBJECTIVES: Real time polymerase chain reaction followed by melting curve analysis using hybridization probes has become an important tool in routine diagnosis of the HFE mutations, which are associated with hereditary hemochromatosis. DESIGN AND METHODS: We used the LightCycler technology for simultaneous detection of the H63D and C282Y mutations of the HFE gene in patients with a higher prevalence for hemochromatosis. RESULTS: In our cohort we identified two siblings with a variant pattern of the HFE-LightCycler melting profiles preventing allelic discrimination. CONCLUSIONS: As a consequence, in these patients DNA sequencing or RFLP analysis is necessary to unequivocally assign the correct HFE genotype.

Amino Acid Substitution↗
PubMed1994

Sick sinus syndrome as the early manifestation of cardiac hemochromatosis.

The most important manifestations of heart disease in hemochromatosis are congestive heart failure and cardiac arrhythmia. The spectrum of disturbances in cardiac rhythm ranges from minor abnormalities on the electrocardiogram to supraventricular arrhythmia, atrioventricular conduction block, and ventricular tachyarrhythmia. Sinus node dysfunction is, however, rarely mentioned. The authors report a case of massive transfusion-induced hemochromatosis in which the patient presented with sick sinus syndrome as the early manifestation of cardiac involvement.

Cardiac Pacing, Artificial↗
PubMed1997

Sustained ventricular tachycardia in cardiac hemochromatosis treated with amiodarone.

Cardiac hemochromatosis can cause heart failure and cardiac arrhythmias. Among these arrhythmias, ventricular tachycardia may be resistant to treatment. A case of cardiac hemochromatosis complicated with ventricular tachycardia that did not respond to intravenous lidocaine, procainamide or propafenone, nor to DC cardioversion, was successfully treated with amiodarone. Amiodarone, a class III antiarrhythmic drug, may be highly effective in similar cases.

Adolescent↗
PubMed1981

Postshunt hemochromatosis with cardiomyopathy.

A case study is reported of a 40 year old male with alcoholic liver disease who, following portacaval shunt, developed hemochromatosis. Biopsy specimens of the liver taken at the time of the shunt and 10 months postoperatively showed no stainable iron. At autopsy, 26 months postoperatively, extensive parenchymal iron deposits were found in the liver, heart, pancreas, thyroid, adrenal, and kidney. Clinically the patient had a cardiomyopathy that in retrospect can be attributed to the cardiac iron deposits. Postshunt hemochromatosis is an infrequently recognized condition that is a potentially reversible cause of cardiac or hepatic decompensation in patients with portacaval shunts.

Adult↗