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At least 847 records · Page 47Linked to original sources
PubMed1997

[Cholangiocarcinoma arising from biliary micro-hamartomas in a man suffering from hemochromatosis].

A case of cholangiocarcinoma arising from multiple bile duct hamartomas (von Meyenburg complexes) is reported in a 68-year-old man. This man has been treated for genetic hemochromatosis for 2 years. The diagnosis of cholangiocarcinoma was suspected by a systematic ultrasound test and made through the pathological examination of the resected specimen. Only six cases have already been reported. Our case is peculiar because it occurred on a genetic hemochromatosis.

Aged↗
PubMed1998

Clinical and pathologic findings in hemochromatosis hip arthropathy.

During a 9-year period, 15 patients with hemochromatosis hip arthropathy required 19 total hip arthroplasties for disabling hip pain. Preoperative presentation, hip function, pathologic evaluation of the femoral head, and radiographic findings were reviewed. Postoperative followup averaging 5.7 years (range, 2-11 years) was performed to assess hip pain and function after total hip arthroplasty. The average preoperative Hospital for Special Surgery hip score was 15 points (range, 4-24 points), and this improved to 30 points (range, 4-38 points) after total hip arthroplasty. Only one of 15 patients required revision surgery at 10 years for acetabular loosening. All other patients were pain free, with improved function at latest followup. Histologic evaluation of the resected femoral heads revealed evidence of primary or secondary osteonecrosis in seven of 19 (37%) specimens. Articular cartilage avulsion at the level of the tidemark was identified in eight of 19 (42%) specimens, and calcium pyrophosphate deposition was identified in five of 19 (26%) specimens. These pathologic findings suggest a predictable progression of the arthritic process in patients with hemochromatosis.

Aged↗
PubMedDate not supplied

[The morphological changes in the internal organs in hemochromatosis].

Visceral changes were studied by histological and electron-microscopic methods in cadavers of 18 subjects dead from hemochromatosis. Pronounced visceral changes in all cases represented a characteristic tetrad of signs: bronze-colored skin, pigmentary cirrhosis of the liver, involvement of the pancreas, and cardiomyopathy. In forensic medical practice hemochromatosis can be found in subjects who were probably genetically predisposed to it and, as a rule, had a history of alcohol abuse. Among the numerous complications of the disease, the most incident are cardiac pathology (dilatation cardiomyopathy) and diabetes mellitus with concomitant intoxications caused by various inflammations.

Autopsy↗
PubMed1998

Lipid peroxidation-induced etheno-DNA adducts in the liver of patients with the genetic metal storage disorders Wilson's disease and primary hemochromatosis.

To assess DNA damage caused by lipid peroxidation due to copper and iron storage disorders in the human liver, the formation of the etheno adducts 1,N6-ethenodeoxyadenosine (epsilon dA) and 3,N4-ethenodeoxycytine (epsilon dC) was measured in liver DNA from normal subjects and from patients with Wilson's disease (WD) and primary hemochromatosis. The mean epsilon dA and epsilon dC levels per 10(9) parent nucleotides in normal liver were 19.3 +/- 4.9 and 27.5 +/- 10.0, respectively. The mean epsilon dA and epsilon dC levels per 10(9) parent nucleotides in WD were 61.03 +/- 7.95 and 91.50 +/- 36.02, and in primary hemochromatosis, they were 46.62 +/- 32.83 and 64.32 +/- 11.55, respectively, two to three times higher than those in the normal liver. The etheno adduct levels were highly correlated with the copper content of the liver in the normal and WD samples. This study demonstrates for the first time the formation of promutagenic etheno adducts in humans in association with copper and iron storage-induced lipid peroxidation. Thus, the etheno adducts are implicated as initiating DNA damage in copper/iron-induced carcinogenesis in humans and should also be explored as biomarkers in disease progression and prevention trials.

Adolescent↗
PubMedDate not supplied

[The use of therapeutic plasmapheresis in the combined therapy of a female patient with idiopathic hemochromatosis].

A patient with idiopathic hemochromatosis has been followed-up for a long time. Methods decreasing serum iron content were used in succession. Five courses of plasmapheresis were administered. The level of serum iron normalized after each course consisting of 3-4 sessions, but the effect was but short-termed. Stable remission could be attained by maintenance desferal therapy after a course of therapeutic plasmapheresis, which can be regarded as a stage in basic therapy for idiopathic hemochromatosis.

Adult↗
PubMed1998

[Molecular biology analysis: hereditary hemochromatosis, Wilson disease, alpha 1-antitrypsin deficiency and Dubin-Johnson syndrome].

The molecular pathology of hereditary hemochromatosis, Wilson's disease, alpha 1-antitrypsin-deficiency and Dubin-Johnson syndrome could be well characterised during the last years. Diagnosis of hereditary hemochromatosis is reliably confirmed by PCR-augmentation and restriction-analysis. Wilson's disease is a monogenetic disease, which is characterised by over 50 mutations. Molecular diagnosis is complicated by the lack of a single specific mutation. Diagnosis of Dubin-Johnson syndrome and alpha 1-antitrypsin-deficiency is possible by PCR-analysis and hybridisation with specific oligonucleotides.

DNA Mutational Analysis↗
PubMed1998

Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthritis.

We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis. His symptoms began at the age of 44 with pain of the hand joints, shoulders, hips, and knees and a positive rheumatoid factor. Four years later, he required replacement of both hips due to severe hip arthritis. Abnormalities in liver function were noted early on, but they were attributed to infection with the hepatitis C virus, detected serologically and by polymerase chain reaction amplification in the blood. The correct diagnosis was delayed until a decision to use methotrexate as treatment for his arthritis led to a liver biopsy, which revealed increased iron deposition consistent with hemochromatosis, confirmed by genetic testing, which revealed that the patient was homozygous for the C282Y mutation of the HLA-H gene.

Adult↗
PubMed1998

Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene.

OBJECTIVE: To determine whether a specific mutation (C282Y) associated with primary hemochromatosis (PHC) is more common in patients with type 2 diabetes than in a control group of patients with type 1 diabetes. Patients with type 2 diabetes have a two- to threefold higher rate of PHC than the general population. Recent identification of a genetic mutation in patients with PHC raises the possibility that the mutation is related to type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS: One hundred and five patients with type 2 diabetes and 103 control patients with type 1 diabetes, who attended the same tertiary care diabetes clinic, who were of European origin, and in whom there was no clinical suspicion of hemochromatosis. INTERVENTIONS: Patients completed a brief clinical assessment and provided a blood sample. Iron studies were measured in serum, and DNA was assayed for the presence of the C282Y and H63D mutations of the HFE gene. RESULTS: Twenty-three of 105 patients (21.9%, 95% confidence interval [CI] 14.0, 29.8) with type 2 diabetes (1 homozygote) and 12 of 103 patients (11.7%; 95% CI 5.5, 17.9) with type 1 diabetes (all heterozygotes) had at least 1 copy of the C282Y mutation (odds ratio [OR] = 2.1; 95% CI 1.0, 4.5; p = 0.048). Neither serum ferritin nor transferrin saturation level identified patients with a C282Y mutation. CONCLUSION: The C282Y gene mutation is a potential genetic marker for type 2 diabetes. It, or a closely linked gene, may be associated with greater than 20% of cases of type 2 diabetes.

Adolescent↗
PubMed2004

Congenital spherocytosis with hereditary hemochromatosis without pathogenic mutations in the HFE gene.

We report a case of an 80-year-old woman with congenital spherocytosis who presented with massive iron overload. Iatrogenic iron overload could be ruled out. Familial history was suggestive of hereditary hemochromatosis; however, molecular genetic testing for the most common HFE mutations remained negative. The patient was treated successfully with phlebotomies. The hypothesis that this patient suffered from hereditary hemochromatosis is discussed on the basis of a brief review of the literature.

Journal Article↗
PubMed2001

A patient with hereditary hemochromatosis, ulcerative colitis, and primary sclerosing cholangitis: genetic aspects.

This report describes a family in which the rare combination of hereditary hemochromatosis, ulcerative colitis and primary sclerosing cholangitis was found. Subsequent to the index patient, who had all three diseases, a screening was done in his parents and siblings that included HLA-DR, HLA-DQ and HFE typing, ANCAs, liver tests and sigmoidoscopy with histology. On the basis of HLA and HFE typing, three probable haplotypes could be distinguished. The genetics of inflammatory bowel disease and hereditary hemochromatosis are discussed.

Journal Article↗
PubMed2006

Liver diseases in the hemochromatosis and iron overload screening study.

BACKGROUND AND AIMS: The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 101,168 primary care participants for iron overload with serum transferrin saturation (TS), ferritin, and C282Y and H63D mutations of the HFE gene. METHODS: All C282Y homozygotes and participants with an increased TS (>45% women, >50% men) and serum ferritin level (> 200 microg/L women, >300 microg/L men) were recalled for a clinical history and physical examination, and blood tests including alanine transaminase (ALT) and aspartate transaminase levels. Hepatitis B surface antigen and anti-hepatitis C virus were measured if the ALT level was increased (>31 IU/L in women, >40 IU/L in men). RESULTS: In the group of participants selected to return for clinical examination because of increased TS and ferritin levels, ALT increases and anti-hepatitis C virus were found in 95 of 284 (33%) African Americans, 50 of 466 (11%) Asian and Pacific Islanders, 21 of 120 (18%) Hispanics, and 40 of 477 (8.4%) Caucasians. ALT increases and hepatitis B surface antigen were detected in 24 of 466 (5%) Asian and Pacific Islanders, 10 of 284 (3.5%) African Americans, 3 of 120 (2.5%) Hispanics, and 2 of 477 (.42%) Caucasians. Of 86 liver biopsy specimens obtained for clinical purposes, 53 were reviewed by a single study pathologist. Liver fibrosis (stage 3 or 4) was present in 2 of 11 (18.2%) C282Y homozygotes that underwent central review and 2 of 302 (.66%) C282Y homozygotes attending the clinical examination. CONCLUSIONS: Screening for iron overload with ferritin and TS detects persons with viral hepatitis and other types of liver disease. A minimum of .66% C282Y homozygotes have liver fibrosis.

Adult↗
PubMed2005

Hemochromatosis and iron-overload screening in a racially diverse population.

BACKGROUND: Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. METHODS: Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. RESULTS: Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 mug per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. CONCLUSIONS: The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.

Arthritis↗
PubMed2006

Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

OBJECTIVE: To assess geographic differences in the frequencies of HFE C282Y and H63D genotypes in six racial/ethnic groups recruited in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. DESIGN: HFE C282Y and H63D genotypes of 97,551 participants, ages > or = 25 years, who reported that they belonged to one of six racial/ethnic groups, were analyzed. HFE genotype frequencies were compared among the racial/ethnic groups and among the HEIRS Study field centers within each racial/ethnic group. RESULTS: The distribution of HFE C282Y and H63D genotypes differed among racial/ethnic groups (P<.0001) and among field centers in Hispanics, Asians, Whites, and Blacks (each P<.05). Genotype frequencies were similar among field centers in Native Americans and Pacific Islanders. Frequencies of C282Y and H63D genotypes were greatest in Whites. The lowest frequencies of C282Y genotypes were observed in Asians; Blacks had the lowest H63D genotype frequencies and the highest frequency of the wild-type genotype. Among racial/ethnic groups, Hispanics had the greatest variation in HFE genotypes across geographic regions. CONCLUSION: HFE C282Y and H63D genotype frequencies vary significantly between racial/ethnic groups and within some racial/ethnic groups across geographic regions.

Adult↗
PubMed2001

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.

Genotype↗
PubMed1998

Hemochromatosis: a genetic defect in iron metabolism.

Hemochromatosis (HC), the common inherited disorder in iron metabolism, affects at least 1 in 300 Caucasians. The disorder causes inappropriately high iron absorption and accumulation of excess iron in the parenchymal cells of the major organs of the body. The gene responsible for HC has recently been cloned and is termed HFE; two missense mutations have been reported in the gene, both cause amino acid substitutions (H63D and C282Y), but to date only the C282Y mutation has been found to clearly correlate with HC in all affected populations. HFE is highly homologous to genes in the major histocompatibility complex (MHC) class I family; all of these genes encode a heterodimeric protein which is complexed to beta 2-microglobulin, a coupling essential for cell surface expression of a functional molecule. The first important step toward establishing the role of HFE in the pathogenesis of HC came with the recent observation that the C282Y mutation disrupts the binding of beta 2-microglobulin to the HFE protein and as a result the mutant molecule is not expressed on the cell surface.

Animals↗
PubMedDate not supplied

Genotype screening for hereditary hemochromatosis among voluntary blood donors in Hungary.

Hereditary hemochromatosis (HH) is a common genetic disorder. Although it is inherited in an autosomal recessive manner, heterozygous individuals are believed to be protected against iron deficiency. Screening to estimate the prevalence of HH was frequently performed among blood donors, not considering that carriers of the HH gene mutations may be present in higher proportion in this population. To examine the allele frequencies of the HH gene (HFE) point mutations, C282Y and H63D genotyping was carried out in 996 consecutive, first-time, and regular Hungarian blood donors by PCR-RFLP techniques. Iron parameters of the first-time donors and the identified C282Y heterozygotes and age, gender, and number of previous blood donation-matched wild-type donors were also determined. We were not able to demonstrate a significant increase in the frequency of C282Y and H63D alleles among regular blood donors, compared to first-time blood donors. However, there was a trend of higher C282Y allele frequency among women with higher number of previous blood donations (2.2 +/- 1.5% in female blood donors with 0-8 previous blood donations compared to 4.8 +/- 2.3% in women with more than 8 previous blood donations, P = 0.06). No detectable phenotypic differences were observed in serum iron, ferritin, and transferrin saturation values between C282Y wild-type and heterozygous groups. However, the single identified C282Y homozygous male (age 21) showed definite signs of iron overload. Our observations suggest that the protective effect of C282Y heterozygosity against iron deficiency may be less significant than other environmental (e.g., iron-rich diet) or genetic factors.

Adolescent↗
PubMed1999

The transferrin receptor binding site on HFE, the class I MHC-related protein mutated in hereditary hemochromatosis.

HFE is a class I major histocompatibility complex (MHC)-related protein that is mutated in patients with the iron storage disease hereditary hemochromatosis. HFE binds tightly to transferrin receptor (TfR), the receptor that mediates uptake of iron-loaded transferrin. The binding affinities for TfR of HFE mutants, designed using the HFE crystal structure, were measured using biosensor assays. The results allow localization of the TfR binding site on HFE to the C-terminal portion of the alpha1 domain helix and an adjacent loop, a region distinct from the ligand binding sites on class I MHC and related proteins. A biosensor-derived pH-dependent affinity profile for the HFE-TfR interaction is discussed in terms of HFE's hypothesized role in intracellular trafficking.

Animals↗
PubMed1999

The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor.

HFE is a class I major histocompatibility complex (MHC)-related protein that is mutated in patients with the iron overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR), the receptor used by cells to obtain iron in the form of diferric transferrin (Fe-Tf). Previous studies demonstrated that HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, and that membrane-bound or soluble HFE binding to cell surface TfR results in a reduction in the affinity of TfR for Fe-Tf. We studied the inhibition by soluble HFE of the interaction between soluble TfR and Fe-Tf using radioactivity-based and biosensor-based assays. The results demonstrate that HFE inhibits the TfR:Fe-Tf interaction by binding at or near the Fe-Tf binding site on TfR, and that the Fe-Tf:TfR:HFE ternary complex consists of one Fe-Tf and one HFE bound to a TfR homodimer.

Binding, Competitive↗