Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HEMOCHROMATOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 685 records · Page 38Linked to original sources
PubMed1986

Neonatal hemochromatosis.

Neonatal hemochromatosis is a specific entity in the spectrum of pediatric liver disease. The clinical course is characterized by progressive deterioration, leading to death within a few days to weeks. The pathologic changes are hepatic fibrosis with massive iron accumulation in hepatocytes. Lesser amounts of iron are found in parenchymal cells of the endocrine organs (adrenal, thyroid, pancreas, pituitary), the heart, and renal tubules. Little iron is present in cells of the reticuloendothelial system. The morphologic pattern thus resembles that of adult idiopathic hemochromatosis. Iron accumulation is a relatively specific finding, as shown by a review of a series of pediatric autopsy cases. Premortem diagnosis of this disease has been made only rarely, and little information is available on laboratory parameters. Recognition of this entity in living neonates is necessary for better understanding of its pathogenesis and treatment.

Female↗
PubMed2002

Concordance of iron indices in homozygote and heterozygote sibling pairs in hemochromatosis families: implications for family screening.

BACKGROUND/AIMS: Concordance of iron indices between same-sex siblings homozygous for the cysteine-to-tyrosine substitution at amino acid 282 (C282Y) mutation suggests that the variable phenotype in hereditary hemochromatosis is caused by genetic factors. Concordance of iron indices between same-sex heterozygous sibling pairs would provide further evidence of genetic modifiers of disease expression, and guidance for family screening strategies of subjects heterozygous for the C282Y mutation. METHODS: We compared the iron indices of 35 C282Y homozygous and 35 C282Y heterozygous same-sex sibling pairs. To clarify whether concordance between siblings was due to environmental or genetic factors we compared the iron indices of 164 C282Y homozygous-normal, same-sex dizygotic twins. RESULTS: Serum ferritin (r=0.50, P=0.003), hepatic iron concentration (r=0.61, P=0.025) and hepatic iron index (r=0.67, P=0.01) were highly concordant in C282Y homozygotes. Heterozygote siblings were concordant for serum ferritin (r=0.76, P=0.0001) and transferrin saturation (r=0.79, P=0.0001). Homozygote-normal same-sex dizygotic twins were concordant for serum ferritin (r=0.62, P=0.0001) but not for transferrin saturation. CONCLUSIONS: Concordance of iron indices exists in C282Y homozygote and heterozygote sibling pairs. Siblings of expressing C282Y heterozygotes require phenotypic assessment. These data provide evidence for modifying genes influencing disease expression in hemochromatosis.

Adolescent↗
PubMed1992

Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection.

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.

Adult↗
PubMed1996

Genetic hemochromatosis in Italian patients with porphyria cutanea tarda: possible explanation for iron overload.

BACKGROUND/AIMS: Mild to moderate iron overload is found in most patients with porphyria cutanea tarda. This study aimed to evaluate whether iron overload in patients with porphyria cutanea tarda is related to the presence of a coexistent genetic hemochromatosis gene. METHODS: A cohort study of 94 Italian patients with porphyria cutanea tarda (90 men and 4 women) and 20 relatives of five patients with iron overload were studied. Diagnosis of iron overload was assessed by transferrin saturation, serum ferritin and iron removed by phlebotomy to reach depletion. HLA typing by microlymphocytotoxicity test and duodenal ferritin analysis by immunohistochemistry were performed in a smaller number of patients. The chi square test was used to compare means and prevalences. RESULTS: Iron overload was present in 62% of the patients. HLA-A3 prevalence was significantly higher (p < 0.01) in subjects with iron overload than in those without. A lack of duodenal ferritin was observed in 14/18 patients with and in 6/12 without iron overload. Family studies showed the presence of iron overload but not of porphyria cutanea tarda in HLA identical or semi-identical relatives of the patients. CONCLUSIONS: Italian patients with porphyria cutanea tarda and iron overload appear to have one or even two genes for genetic hemochromatosis.

Adult↗
PubMed1997

[Cardiac pathology of extracardiac origin (II). The cardiac repercussion of amyloidosis and hemochromatosis].

Although rare, amyloidosis and hemochromatosis are the infiltrative diseases in which the heart is more frequently involved. The most common clinical presentation is heart failure with hemodynamic features of restrictive heart disease in cardiac amyloidosis. The diagnosis is often made because of symptoms of other organ involvement, although sometimes cardiac symptoms may be the initial manifestation. The non-specific clinical presentation and the low prevalence of these cardiomyopathies make the diagnosis difficult if the clinician does not suspect it. Once symptoms develop, the evolution is fast. Usually, the unsatisfactory and ineffective treatment of amyloidosis and hemochromatosis contribute to the poor prognosis. The indication of cardiac transplantation in advanced cases is questionable because of the high recurrence of the illness.

Amyloidosis↗
PubMed2003

Neonatal hemochromatosis.

Neonatal hemochromatosis is a rare gestational condition in which iron accumulates in the fetal tissues in a distribution like that seen in hereditary hemochromatosis. Extensive liver damage is the dominant clinical feature, with late fetal loss or early neonatal death. NH recurs within sibships at a rate higher than that predicted for simple Mendelian autosomal-recessive inheritance, possibly suggesting the role of a maternal factor. Immunomodulation during pregnancy at risk appears to lessen the severity of disease.

Female↗
PubMed1999

Quantitative determination of 8-hydroxy-2'-deoxyguanosine in human urine by isotope dilution mass spectrometry: normal levels in hemochromatosis.

A previously developed method for quantitative determination of 8-hydroxyguanine by gas chromatography-mass spectrometry was modified to allow measurement of 8-hydroxy-2'-deoxyguanosine in human urine. [4,5,6,8-(13)C4]8-Hydroxy-2'-deoxyguanosine was prepared by enzymatic coupling of [4,5,6,8-(13)C4]8-hydroxyguanine to deoxyribose-1-phosphate. Samples of human urine (2 ml) were spiked with the labeled nucleoside (13 nmol) and subjected to solid phase extraction and reversed phase high performance liquid chromatography. The 8-hydroxy-2'-deoxyguanosine thus isolated was hydrolyzed by treatment with aqueous formic acid, and the resulting 8-hydroxyguanine was converted into its tetrakis-trimethylsilyl derivative and subjected to gas-liquid chromatographic-mass spectrometric analysis. Repeated determinations of 8-hydroxy-2'-deoxyguanosine in pools of urine showed coefficients of variation of 5 and 8% at concentrations of 8-hydroxy-2'-deoxyguanosine equal to 18 and 2 nM, respectively. Determination of 8-hydroxy-2'-deoxyguanosine in samples of urine spiked with different amounts of the unlabeled nucleoside showed a mean recovery of 102%. Application of the analytical method to a group of 11 apparently healthy subjects (mean age, 47 years) showed a mean level of endogenously produced 8-hydroxy-2'-deoxyguanosine equal to 1.33 +/- 0.29 micromol/mol creatinine. The level recorded for another group of 15 younger subjects (mean age, 28 years) was somewhat higher, that is, 1.58 +/- 0.84 micromol/mol creatinine, corresponding to a 24-h production rate of 8-hydroxy-2'-deoxyguanosine equal to 20.6 +/- 11.6 nmol (288 +/- 140 pmol/24 h x kg body weight). Hemochromatosis is a hereditary disease characterized by increased absorption of iron from the gastrointestinal tract and deposition of iron in organs. Application of the analytical method to a group of 12 patients with hereditary hemochromatosis who were under treatment with venesections showed a mean level of urinary 8-hydroxy-2'-deoxyguanosine equal to 1.39 +/- 0.40 micromol/mol creatinine. This value was not significantly different from those of healthy subjects. The fact that these patients had only slight or moderate iron overload at the time of urinary sample collection may have influenced the urinary levels of 8-hydroxy-2'-deoxyguanosine in the present study.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1987

Sicca symptom in a patient with hemochromatosis: minor salivary gland biopsy for differential diagnosis.

This paper reports a case of hemochromatosis with sicca symptom. The patient was a 59-year-old female who had been received a series of intravenous iron injections and blood transfusions because of anemia owing to side-effects of a chemotherapeutic agent. She complained of dry mouth and dry eyes in addition to symptoms of hemochromatosis. The histological appearance of the labial salivary gland, with heavy deposition of iron in acinar and duct epithelial cells and absence of focal lymphoid cell infiltration, did not support a diagnosis of Sjögren's syndrome but suggested functional damage of the salivary glands related to iron. The patient was given desferrioxamine, and clinical symptoms improved; re-examined labial salivary gland biopsy showed no iron deposition in any parenchymal cells after the treatment.

Atrophy↗
PubMed1997

Liver transplantation for hemochromatosis, Wilson's disease, and other metabolic disorders.

Liver transplantation provides an effective means for replacing a failing liver, in addition to correcting the underlying abnormality in many metabolic disorders. Results of liver transplantation for metabolic diseases have been generally encouraging, with the exception of hereditary hemochromatosis, in which infectious and cardiac complications appear to increase post-transplant mortality. Better pretransplant diagnosis of hemochromatosis, utilizing the recently identified putative gene, may help reduce post-transplant complications. In metabolic diseases, improved understanding of the underlying genetic and molecular defects will lead to advances in medical therapy and perhaps a decreased need for liver transplantation. NTBC therapy for hereditary tyrosinemia and purified glucocerebroside therapy for Gaucher disease are two such examples. The prospects of gene therapy are being actively pursued for many metabolic diseases, such as CF, hemophilia, and familial hypercholesterolemia. Until such investigation leads directly to clinical practice, however, liver transplantation remains an effective option for therapy for a wide range of metabolic diseases.

Hemochromatosis↗
PubMed2001

Hemochromatosis mutations C282Y and H63D in 'cis' phase.

Homozygosity for the C282Y mutation of the HFE gene is a highly significant risk factor for the development of hereditary hemochromatosis (HH) and the majority of patients with HH have this genotype. An Irish/Belgian female with an elevated serum ferritin level and a family history of hemochromatosis was tested for the presence of the C282Y and H63D mutations. Results of digested PCR products have shown the patient to be homozygous for C282Y mutation and heterozygous for H63D mutation. Sequencing confirmed these findings. Genotyping of the patient's offspring and husband has also indicated the inheritance of both C282Y and H63D in 'cis'. Implications of this finding are: 1) the compound heterozygous state is by far the most common, but not the universal, phase for individuals found to be heterozygous for the two mutations, C282Y and H63D; 2) the C282Y and H63D mutations in the 'cis' phase may account for some cases of questionable parentage.

Aged↗
PubMed2001

A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.

Hereditary hemochromatosis (HH) is a very common disorder characterized by iron overload and multi-organ damage. Several genes involved in iron metabolism have been implicated in the pathology of HH (refs. 1-4). We report that a mutation in the gene encoding Solute Carrier family 11, member A3 (SLC11A3), also known as ferroportin, is associated with autosomal dominant hemochromatosis.

Amino Acid Sequence↗
PubMed2001

MCV as a guide to phlebotomy therapy for hemochromatosis.

BACKGROUND: A multitude of recommendations exist for laboratory assays to monitor the pace and endpoints of phlebotomy therapy for hemochromatosis. All of these recommendations rely on an assessment of storage iron to guide treatment, and none have been prospectively evaluated. STUDY DESIGN AND METHODS: Nine consecutive patients underwent serial monitoring of Hb, MCV, transferrin saturation, and ferritin during weekly phlebotomy to deplete iron stores (induction therapy) and less frequent sessions to prevent iron reaccumulation (maintenance therapy). Changes in MCV and Hb were used to guide the pace of phlebotomy over a median of 7 years of follow-up. RESULTS: During induction therapy, the MCV increased transiently because of reticulocytosis and then stabilized for a prolonged period before decreasing more sharply, which reflected iron-limited erythropoiesis. Iron depletion was achieved after a median of 38 phlebotomies and removal of 9.0 g of iron. Maintenance phlebotomy was targeted to maintain the MCV at 5 to 10 percent below prephlebotomy values and the Hb at >13 g per dL. Transferrin saturation fluctuated considerably during treatment, but remained below 35 percent during MCV-guided maintenance therapy. Ferritin values were not useful guides to the pace of phlebotomy. The median maintenance therapy phlebotomy interval was 7.5 weeks (range, 6-16), which corresponded to an average daily iron removal of 35 to 67 microg per kg. Most patients showed evidence of iron reaccumulation at phlebotomy intervals of 8 weeks or more. CONCLUSION: The MCV is an inexpensive, precise, physiologic indicator of erythropoietic iron availability. When used in conjunction with the Hb, it is a clinically useful guide to the pace of phlebotomy therapy for hemochromatosis.

Adult↗
PubMed2006

Hepatocellular carcinoma associated with hereditary hemochromatosis occurring in non-cirrhotic liver.

The occurrence of primary hepatocellular carcinoma (HCC) in patients with hereditary hemochromatosis (HH) is well known. Thereby, the development of liver cirrhosis seems to be a prerequisite. Whether or not a hepatic iron overload in the context of hereditary hemochromatosis is an independent risk factor for HCC remains unclear. To date there are only a few reports about HCC arising in non-cirrhotic livers in the presence of HH. We report the case of a 64-year-old man who presented to our outpatient clinic with HCC. Liver cirrhosis could be excluded. Detailed exploration of the patient's history revealed that he had been treated by venesection for about 10 years up to 15 years ago. Subsequent investigations showed an elevated serum ferritin and transferrin saturation. The diagnosis of HH was confirmed by genetic testing, with homozygosity for the Cys282Tyr mutation. The patient received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC.

Carcinoma, Hepatocellular↗
PubMed2005

Clinical aspects of hemochromatosis.

The term hemochromatosis is commonly used as synonymous with HFE-associated genetic iron overload but several rarer causes of an identical clinicopathological syndrome have been described in recent years. The most common symptoms are lethargy and arthralgia, and the major complications of end-stage disease are cirrhosis, diabetes, and cardiac and endocrine manifestations. However, with the development of cascade screening for family members of affected probands as well as screening for common diseases at health checks, hemochromatosis is being detected at increasingly early stages, often when there are only biochemical abnormalities. The available evidence from screening studies strongly suggests that approximately 75% of C282Y homozygous subjects have biochemical expression. Hepatic iron overload is present in approximately 56% and 34% of men and women, respectively, advanced hepatic fibrosis in 18.7% and 5.4%, respectively, and cirrhosis in 5.8% and 1.9%, respectively. In subjects with severe expression of the disease, additional modifying genetic mutations have been described including those in hepcidin and hemojuvelin. Treatment is by regular phlebotomy which, if instituted before the development of cirrhosis, results in normal life expectancy.

Genetic Predisposition to Disease↗
PubMed1976

Normal serum ferritin concentrations in precirrhotic hemochromatosis.

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Adult↗
PubMed1977

Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease.

We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.

Adolescent↗
PubMed1979

Hereditary hemochromatosis. Phenotypic expression of the disease.

Previous studies have shown that hemochromatosis is an inherited, autosomal-recessive disease and that the gene is closely linked to the HLA locus on chromosome 6. We obtained a lod score for linkage of +9.8 for a recombination fraction of 0.0 and a gene frequency of 0.056, the frequency estimated in this population. We studied the phenotypic expression of the disease in 261 members of 10 pedigrees. In heterozygotes over 20 years of age, there was an intermediate increase in transferrin saturation and a limited increase in hepatic iron but no clinical manifestations. In male heterozygotes, the average amount of iron in the liver increased from about 0.2 to 1.3 g. Abnormal homozygotes accumulated iron progressively with time, with men accumulating about 18 g in the liver. All measurements of iron status were increased in abnormal homozygotes. Hemochromatosis is inherited as an autosomal-recessive disease, with partial biochemical expression in heterozygotes.

Adolescent↗
PubMed1985

Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis.

We analyzed survival and causes of death among 163 patients with primary hemochromatosis diagnosed between 1959 and 1983. The mean follow-up period was 10.5 +/- 5.6 years (+/- S.D.). Cumulative survival was 92 per cent at 5 years, 76 per cent at 10 years, 59 per cent at 15 years, and 49 per cent at 20 years. Life expectancy was reduced in patients with cirrhosis of the liver as compared with those without cirrhosis (P less than or equal to 0.05), in patients with diabetes mellitus as compared with those without diabetes (P less than or equal to 0.002), and in patients who could not be depleted of iron during the first 18 months of venesection therapy as compared with those who could be depleted (P less than or equal to 0.001). Prognosis was not influenced by sex (P less than or equal to 0.5). Patients without cirrhosis had a life expectancy that was not different from that expected in an age- and sex-matched normal population. Analysis of the causes of death in 53 patients, as compared with the normal population, showed that liver cancer was 219 times more frequent among the patients (16 patients), cardiomyopathy was 306 times more frequent (3 patients), liver cirrhosis was 13 times more frequent (10 patients), and diabetes mellitus was 7 times more frequent (3 patients). Death rates for other causes, including extrahepatic carcinomas (seven patients), were not different from the rates expected. We conclude that patients with hemochromatosis diagnosed in the precirrhotic stage and treated by venesection have a normal life expectancy, whereas cirrhotic patients have a shortened life expectancy and a high risk of liver cancer even when complete iron depletion has been achieved.

Adolescent↗