381 results on '"Hemochromatosis physiopathology"'
Search Results
2. New Mutations in HFE2 and TFR2 Genes Causing Non HFE -Related Hereditary Hemochromatosis.
- Author
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Hernández G, Ferrer-Cortès X, Venturi V, Musri M, Pilquil MF, Torres PMM, Rodríguez IH, Mínguez MÀR, Kelleher NJ, Pelucchi S, Piperno A, Alberca EP, Ricós GG, Giró EC, Pérez-Montero S, Tornador C, Villà-Freixa J, and Sánchez M
- Subjects
- Adult, Codon, Nonsense genetics, Female, GPI-Linked Proteins metabolism, Hemochromatosis physiopathology, Hemochromatosis Protein metabolism, Histocompatibility Antigens Class I metabolism, Humans, Iron metabolism, Liver metabolism, Male, Membrane Proteins genetics, Middle Aged, Pedigree, Receptors, Transferrin metabolism, GPI-Linked Proteins genetics, Hemochromatosis genetics, Hemochromatosis Protein genetics, Receptors, Transferrin genetics
- Abstract
Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases. Here, we describe six new patients of non-HFE related HH from five different families. Two families (Family 1 and 2) have novel nonsense mutations in the HFE2 gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). Three families have mutations in the TFR2 gene, one case has one previously unreported mutation (Family A-p.Asp680Tyr) and two cases have known pathogenic mutations (Family B and D-p.Trp781Ter and p.Gln672Ter respectively). Clinical, biochemical, and genetic data are discussed in all these cases. These rare cases of non-HFE related hereditary hemochromatosis highlight the importance of an earlier molecular diagnosis in a specialized center to prevent serious clinical complications.
- Published
- 2021
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3. Hereditary Hemochromatosis: Rapid Evidence Review.
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Kane SF, Roberts C, and Paulus R
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- Hemochromatosis epidemiology, Hemochromatosis physiopathology, Humans, Liver Cirrhosis blood, Liver Cirrhosis etiology, Mass Screening methods, Transferrin analysis, Hemochromatosis diagnosis
- Abstract
Hereditary hemochromatosis is an autosomal recessive disorder that disrupts iron homeostasis, resulting in systemic iron overload. It is the most common inherited disorder among people of northern European ancestry. Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance. The deposition of excess iron into parenchymal cells leads to cellular dysfunction and the clinical manifestations of the disease. The liver, pancreas, joints, heart, skin, and pituitary gland are the most commonly involved organs. Hereditary hemochromatosis is usually diagnosed in the 40s or 50s. Women are often diagnosed later than men, likely because of menstrual blood loss. There is no typical presentation or pathognomonic signs and symptoms of hereditary hemochromatosis. Because of increased awareness and earlier diagnosis, the end-organ damage secondary to iron overload is not often seen in clinical practice. A common initial presentation is an asymptomatic patient with mildly elevated liver enzymes who is subsequently found to have elevated serum ferritin and transferrin saturation. Ferritin levels greater than 300 ng per mL for men and 200 ng per mL for women and transferrin saturations greater than 45% are highly suggestive of hereditary hemochromatosis. Phlebotomy is the mainstay of treatment and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications. Liver transplantation may be considered in select patients. Individuals with hereditary hemochromatosis have an increased risk of hepatocellular carcinoma and colorectal and breast cancers. Genetic testing for the hereditary hemochromatosis genes should be offered after 18 years of age to first-degree relatives of patients with the condition.
- Published
- 2021
4. Hemochromatoses.
- Author
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Brissot P and Loréal O
- Subjects
- Hemochromatosis physiopathology, Humans, Iron Overload complications, Iron Overload physiopathology, Hemochromatosis diagnosis
- Abstract
Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
- Published
- 2021
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5. Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders.
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Xu Y, Alfaro-Magallanes VM, and Babitt JL
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- Animals, Humans, Anemia, Iron-Deficiency genetics, Anemia, Iron-Deficiency metabolism, Anemia, Iron-Deficiency pathology, Anemia, Iron-Deficiency physiopathology, Erythropoiesis, Hemochromatosis genetics, Hemochromatosis metabolism, Hemochromatosis pathology, Hemochromatosis physiopathology, Hepcidins blood, Hepcidins genetics, Liver metabolism, Liver pathology, Liver physiopathology
- Abstract
The discovery of hepcidin has provided a solid foundation for understanding the mechanisms of systemic iron homeostasis and the aetiologies of iron disorders. Hepcidin assures the balance of circulating and stored iron levels for multiple physiological processes including oxygen transport and erythropoiesis, while limiting the toxicity of excess iron. The liver is the major site where regulatory signals from iron, erythropoietic drive and inflammation are integrated to control hepcidin production. Pathologically, hepcidin dysregulation by genetic inactivation, ineffective erythropoiesis, or inflammation leads to diseases of iron deficiency or overload such as iron-refractory iron-deficiency anaemia, anaemia of inflammation, iron-loading anaemias and hereditary haemochromatosis. In the present review, we discuss recent insights into the molecular mechanisms governing hepcidin regulation, how these pathways are disrupted in iron disorders, and how this knowledge is being used to develop novel diagnostic and therapeutic strategies., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2021
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6. Clinical evaluation of infiltrative cardiomyopathies resulting in heart failure with preserved ejection fraction.
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Madan N and Kalra D
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- Amyloidosis complications, Amyloidosis physiopathology, Amyloidosis therapy, Cardiomyopathies complications, Cardiomyopathies physiopathology, Cardiomyopathies therapy, Diagnosis, Differential, Early Diagnosis, Fabry Disease complications, Fabry Disease physiopathology, Fabry Disease therapy, Heart Failure diagnostic imaging, Heart Failure physiopathology, Heart Failure therapy, Hemochromatosis complications, Hemochromatosis physiopathology, Hemochromatosis therapy, Humans, Predictive Value of Tests, Prognosis, Amyloidosis diagnostic imaging, Cardiomyopathies diagnostic imaging, Fabry Disease diagnostic imaging, Heart Failure etiology, Hemochromatosis diagnostic imaging, Stroke Volume, Ventricular Function, Left
- Abstract
Heart failure with preserved ejection fraction is a very common clinical problem. Its prevalence is increasing with aging of the population. A diverse group of risk factors and etiologies comprise the HFpEF syndrome. No specific therapies have been shown to improve survival for the vast majority of HFpEF cases. Restrictive cardiomyopathies account for a significant portion of HFpEF patients and are characterized by diastolic dysfunction due to infiltration of the myocardium or ventricular hypertrophy. Many of these restrictive diseases occur in the context of myocardial infiltration by other substances such as amyloid, iron or glycogen or endomyocardial fibrosis. These infiltrative diseases usually have important clues in the clinical picture and on cardiac imaging that may allow differentiation from the usual HFpEF phenotype (that is commonly seen in the older, hypertensive patient). Noninvasive diagnosis has replaced endomyocardial biopsy for most instances in the workup of these conditions. Early recognition is important to institute specific therapies and to improve prognosis. In this review, we describe 4 major infiltrative cardiomyopathies (Cardiac Amyloidosis, Sarcoidosis, Hemochromatosis and Fabry disease), and their key imaging features., Competing Interests: The authors declare no conflicts of interest., (© 2020 Madan and Kalra Published by IMR press.)
- Published
- 2020
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7. Comparing Care of the Primary and Secondary Hemochromatosis Patients.
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Becker S
- Subjects
- Hemochromatosis blood, Hemochromatosis genetics, Hemochromatosis physiopathology, Humans, Iron blood, Mutation genetics, Deferiprone therapeutic use, Deferoxamine therapeutic use, Hemochromatosis drug therapy, Iron adverse effects, Iron Chelating Agents therapeutic use, Siderophores therapeutic use
- Abstract
Hemochromatosis is an imbalance of excessive serum iron and is a life-threatening condition if left untreated. Due to different causes, primary and secondary hemochromatosis have different patient care considerations for the infusion nurse. Understanding the pathophysiology and how the body absorbs iron is imperative for providing the highest quality care. Since primary (hereditary) hemochromatosis originates from a gene mutation, and secondary (acquired) from excessive intake, the treatment and education must be adjusted accordingly to deliver successful outcomes for both diagnoses.
- Published
- 2020
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8. Liver disease and heart failure.
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Correale M, Tricarico L, Leopizzi A, Mallardi A, Mazzeo P, Tucci S, Grazioli D, Di Biase M, and Brunetti ND
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- Acute Disease, Fabry Disease physiopathology, Glycogen Storage Disease physiopathology, Hemochromatosis physiopathology, Hemodynamics, Hemosiderosis physiopathology, Hepatitis complications, Hepatolenticular Degeneration physiopathology, Humans, Inflammation, Ischemia pathology, Liver Function Tests, Heart Failure complications, Liver Diseases complications
- Abstract
Introduction: Several systemic conditions, inflammatory disease, infections and alcoholism, may affect both the heart and the liver. Common conditions, such as the non-alcoholic fatty liver disease (NAFLD), may increase the risk of cardiac dysfunction. Patients with acute decompensated HF (ADHF) may develop acute ischemic hepatitis and, chronic HF patients may develop congestive hepatopathy (CH)., Evidence Acquisition: Laboratory anomalies of hepatic function may predict the outcome of patients with advanced HF and the evaluation of both cardiac and hepatic function is very important in the management of these patients. In clinically apparent ischemic hepatitis more than 90% of patients have some right-sided HF. There are systemic disorders characterized by the accumulation of metals or by metabolism defects that may affect primarily the liver but also the heart leading to symptomatic hypertrophic cardiomyopathy (HCM)., Evidence Synthesis: Abnormal LFTs indicate the mechanism of liver injury: liver congestion or liver ischemia. In AHF, it's important an adequate evaluation of heart and liver function in order to choose the treatment in order to ensure stable hemodynamic as well as optimal liver function., Conclusions: Measurements of LFTs should be recommended in the early phase of ADHF management. Physicians with interest in HF should be trained in the evaluation of LFTs. It's very important for cardiologists to know the systemic diseases affecting both heart and liver and the first imaging or laboratory findings useful for a diagnosis. it is very important for internists, nephrologists, cardiologists, primary physicians and any physicians with interest in treating HF to recognize such signs and symptoms belong to rare diseases and liver diseases that could be mistaken for HF.
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- 2020
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9. Progressive splenomegaly and mild thrombocytosis in beta-thalassaemia trait and coexisting hereditary hemochromatosis: possible confounders for a subsequent hematological diagnosis.
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Pelusi S, Iuculano F, Lombardi R, Francione P, Gianelli U, Fracanzani AL, and Fargion S
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- Alcohol Drinking adverse effects, Alcohol Drinking psychology, Female, Hemochromatosis physiopathology, Humans, Middle Aged, Phlebotomy methods, beta-Thalassemia physiopathology, Hemochromatosis complications, Splenomegaly diagnosis, Thrombocytosis diagnosis, beta-Thalassemia genetics
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- 2019
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10. [Neonatal haemochromatosis: 10 years into a paradigm shift].
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García Victori E, Mañas R, Castilla Fernández Y, Ruiz Campillo CW, and Castillo Salinas F
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- Female, Hemochromatosis diagnosis, Hemochromatosis physiopathology, Humans, Infant, Newborn, Male, Retrospective Studies, Hemochromatosis therapy
- Published
- 2019
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11. HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.
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Oppl B, Husar-Memmer E, Pfefferkorn S, Blank M, Zenz P, Gollob E, Wurnig C, Engel A, Stadlmayr A, Uyanik G, Brozek W, Klaushofer K, Zwerina J, and Datz C
- Subjects
- Aged, Arthroplasty, Replacement methods, Female, Ferritins blood, Genotype, Hemochromatosis complications, Hemochromatosis physiopathology, Hemochromatosis surgery, Humans, Iron Overload complications, Iron Overload physiopathology, Male, Middle Aged, Mutation, Osteoarthritis, Hip complications, Osteoarthritis, Hip physiopathology, Osteoarthritis, Hip surgery, Severity of Illness Index, Hemochromatosis diagnosis, Hemochromatosis Protein genetics, Iron Overload diagnosis, Osteoarthritis, Hip diagnosis
- Abstract
Objective: Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis., Methods: In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls., Results: No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population., Conclusion: Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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12. Can two-dimensional speckle tracking echocardiography be useful for left ventricular assessment in the early stages of hereditary haemochromatosis?
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Rozwadowska K, Daniłowicz-Szymanowicz L, Fijałkowski M, Sikorska K, Gałąska R, Kozłowski D, Gruchała M, and Raczak G
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- Adult, Female, Heart Ventricles diagnostic imaging, Heart Ventricles physiopathology, Humans, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Echocardiography methods, Hemochromatosis complications, Hemochromatosis physiopathology, Ventricular Dysfunction, Left etiology, Ventricular Dysfunction, Left physiopathology
- Abstract
Background: Hereditary haemochromatosis (HH) is a common inherited disease. Abnormally increased intestinal iron absorption and accelerated recycling of iron by macrophages lead to progressive body iron accumulation and the generation of oxidative stress. In the late stages, iron overload can lead to dysfunction of the left ventricle (LV). It is believed that two-dimensional speckle tracking echocardiography (2D STE) can evaluate LV dysfunction more accurately than conventional echocardiography. This accurate evaluation seems to be clinically important in the early stages of HH before substantial damage of the LV. Evaluation of this assessment was the purpose of this paper., Methods: We prospectively enrolled 24 patients with early diagnosed HH and without any history of cardiovascular diseases; 23 healthy age- and sex-matched volunteers constituted the control group. Standard echocardiographic parameters and LV rotation and strain parameters were assessed and compared between the groups., Results: All echocardiographic parameters were within normal ranges, and there were no differences between the groups. 2D STE revealed significantly worse basal and apical rotation, twist and torsion values in HH patients. The peak systolic longitudinal strain was decreased in HH patients, even though the LV ejection fraction (LVEF) was normal. There were weak correlations between the iron turnover and 2D STE parameters., Conclusions: 2D STE seems to be more sensitive than traditional echocardiography for detecting LV abnormalities in HH patients who are diagnosed early. The results of this study may be clinically useful, but their relevance and therapeutic implications remain to be confirmed by further studies., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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13. Hemochromatosis: pathophysiology, evaluation, and management of hepatic iron overload with a focus on MRI.
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Golfeyz S, Lewis S, and Weisberg IS
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- Hemochromatosis etiology, Hemochromatosis physiopathology, Humans, Iron metabolism, Iron Overload diagnosis, Iron Overload therapy, Liver physiopathology, Magnetic Resonance Imaging methods, Hemochromatosis diagnosis, Hemochromatosis therapy, Liver diagnostic imaging
- Abstract
Introduction: Hereditary hemochromatosis (HH) is an autosomal recessive disorder that occurs in approximately 1 in 200-250 individuals. Mutations in the HFE gene lead to excess iron absorption. Excess iron in the form of non-transferrin-bound iron (NTBI) causes injury and is readily uptaken by cardiomyocytes, pancreatic islet cells, and hepatocytes. Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure. Untreated hemochromatosis can lead to chronic liver disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Many invasive and noninvasive diagnostic tests are available to aid in diagnosis and treatment. MRI has emerged as the reference standard imaging modality for the detection and quantification of hepatic iron deposition, as ultrasound (US) is unable to detect iron overload and computed tomography (CT) findings are nonspecific and influenced by multiple confounding variables. If caught and treated early, HH disease progression can significantly be altered. Area covered: The data on Hemochromatosis, iron overload, and MRI were gathered by searching PubMed. Expert commentary: MRI is a great tool for diagnosis and management of iron overload. It is safe, effective, and a standard protocol should be included in diagnostic algorithms of future treatment guidelines.
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- 2018
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14. Osteoporosis in chronic liver disease.
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Guañabens N and Parés A
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- Adaptor Proteins, Signal Transducing, Alcoholism complications, Bilirubin metabolism, Bone Density drug effects, Bone Morphogenetic Proteins physiology, Cholestasis complications, Chronic Disease, Cytokines physiology, Diphosphonates therapeutic use, Fractures, Bone complications, Genetic Markers physiology, Hemochromatosis physiopathology, Humans, Liver Diseases complications, Osteoporosis complications
- Abstract
Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in chronic cholestasis, in addition to non-alcoholic fatty liver disease, haemochromatosis and alcoholism. Mechanisms underlying osteoporosis are poorly understood, but osteoporosis mainly results from low bone formation. In this setting, sclerostin, a key regulator of the Wnt/β-catenin signalling pathway which regulates bone formation, in addition to the effects of the retained substances of cholestasis such as bilirubin and bile acids on osteoblastic cells, may influence the decreased bone formation in chronic cholestasis. Similarly, the damaging effects of iron and alcohol on osteoblastic cells may partially explain bone disease in haemochromatosis and alcoholism. A role for proinflammatory cytokines has been proposed in different conditions. Increased bone resorption may occur in cholestatic women with advanced disease. Low vitamin D, poor nutrition and hypogonadism, may be contributing factors to the full picture of bone disorders in chronic liver disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
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15. Do pregnancies reduce iron overload in HFE hemochromatosis women? results from an observational prospective study.
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Scotet V, Saliou P, Uguen M, L'Hostis C, Merour MC, Triponey C, Chanu B, Nousbaum JB, Le Gac G, and Ferec C
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- Adult, Alcohol Drinking epidemiology, Alcohol Drinking physiopathology, Body Mass Index, Female, Ferritins blood, France epidemiology, Hemochromatosis Protein genetics, Homozygote, Humans, Iron Overload diagnosis, Iron Overload etiology, Male, Menopause blood, Middle Aged, Pregnancy, Regression Analysis, Risk Factors, Sex Factors, Hemochromatosis diagnosis, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis therapy, Iron blood, Phlebotomy methods, Phlebotomy statistics & numerical data, Pregnancy Complications, Hematologic diagnosis, Pregnancy Complications, Hematologic genetics, Pregnancy Complications, Hematologic physiopathology, Pregnancy Complications, Hematologic therapy
- Abstract
Background: HFE hemochromatosis is an inborn error of iron metabolism linked to a defect in the regulation of hepcidin synthesis. This autosomal recessive disease typically manifests later in women than men. Although it is commonly stated that pregnancy is, with menses, one of the factors that offsets iron accumulation in women, no epidemiological study has yet supported this hypothesis. The aim of our study was to evaluate the influence of pregnancy on expression of the predominant HFE p.[Cys282Tyr];[Cys282Tyr] genotype., Methods: One hundred and forty p.Cys282Tyr homozygous women enrolled in a phlebotomy program between 2004 and 2011 at a blood centre in western Brittany (France) were included in the study. After checking whether the disease expression was delayed in women than in men in our study, the association between pregnancy and iron overload was assessed using multivariable regression analysis., Results: Our study confirms that women with HFE hemochromatosis were diagnosed later than men cared for during the same period (52.6 vs. 47.4 y., P < 0.001). Compared to no pregnancy, having at least one pregnancy was not associated with lower iron markers. In contrast, the amount of iron removed by phlebotomies appeared significantly higher in women who had at least one pregnancy (e
β = 1.50, P = 0.047). This relationship disappeared after adjustment for confounding factors (eβ = 1.35, P = 0.088)., Conclusions: Our study shows that pregnancy status has no impact on iron markers level, and is not in favour of pregnancy being a protective factor in progressive iron accumulation. Our results are consistent with recent experimental data suggesting that the difference in disease expression observed between men and women may be explained by other factors such as hormones.- Published
- 2018
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16. Haemochromatosis: Pathophysiology and the red blood cell1.
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Richardson KJ, McNamee AP, and Simmonds MJ
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- Hemochromatosis physiopathology, Humans, Male, Erythrocytes metabolism, Hemochromatosis diagnosis, Iron metabolism, Rheology methods
- Abstract
Haemochromatosis remains the most prevalent genetic disorder of Caucasian populations in Australia and the United States, occurring in ∼1 of 200 individuals and having a carrier frequency of 10-14%. Hereditary haemochromatosis is an autosomal recessive condition, that is phenotypically characterised by a gradual accumulation of iron, above and beyond that required for biological function. Once the binding capacity of iron carriers reaches saturation, the highly reactive free iron generates radicals that may lead to widespread cellular dysfunction. Thus, the compounding effects of systemic iron overload and the associated oxidative stress in untreated haemochromatosis patients results in tissue damage precipitating severe complications, including: liver cirrhosis, hepatocellular cancer, cardiomyopathy, and diabetes. The primary treatment indicated for individuals with haemochromatosis is venesection therapy (i.e., regular bloodletting of ∼450 mL). Given the frequency of venesection required to decrease and normalise the elevated iron levels, this population may serve as a valuable source of blood products which are in short supply. While the complications associated with elevated iron deposits are frequently reported, the influence of haemochromatosis on the rheological properties of blood and red blood cells (RBC) - major determinants of microvascular blood flow and tissue perfusion - are poorly understood. Limited studies investigating haemorheology in patients with haemochromatosis have reported altered physical properties of blood, which may partly explain the comorbidities associated with the disorder. The current review will explore the aetiology, pathology, and clinical implications of haemochromatosis disease and the associated oxidative stress, with particular emphasis on RBC.
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- 2018
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17. Nonrheumatoid Arthritis of the Hand.
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Lans J, Machol JA 4th, Deml C, Chen NC, and Jupiter JB
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- Arthritis surgery, Arthroplasty, Arthroscopy, Chondrocalcinosis physiopathology, Chondrocalcinosis surgery, Diabetes Complications physiopathology, Diabetes Complications surgery, Gout physiopathology, Gout surgery, Hand Joints surgery, Hemochromatosis physiopathology, Hemochromatosis surgery, Hepatitis C, Chronic physiopathology, Hepatitis C, Chronic surgery, Humans, Arthritis physiopathology, Hand Joints physiopathology
- Abstract
Arthropathy of the hand is commonly encountered. Contributing factors such as aging, trauma, and systemic illness all may have a role in the evolution of this pathology. Besides rheumatoid arthritis, other diseases affect the small joints of the hand. A review of nonrheumatoid hand arthropathies is beneficial for clinicians to recognize these problems., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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18. Genetic hemochromatosis: Pathophysiology, diagnostic and therapeutic management.
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Brissot P, Cavey T, Ropert M, Guggenbuhl P, and Loréal O
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- Hemochromatosis diagnosis, Hemochromatosis physiopathology, Hemochromatosis therapy, Hepcidins physiology, Humans, Iron metabolism, Hemochromatosis genetics
- Abstract
The term hemochromatosis (HC) corresponds to several diseases characterized by systemic iron overload of genetic origin and affecting both the quality of life and life expectancy. Major improvement in the knowledge of iron metabolism permits to divide these diseases into two main pathophysiological categories. For most HC forms (types 1, 2, 3 and 4B HC) iron overload is related to cellular hepcidin deprivation which causes an increase of plasma iron concentration and the appearance of plasma non-transferrin bound iron. In contrast, iron excess in type 4A ferroportin disease is related to decreased cellular iron export. Whatever the HC type, the diagnosis rests on a non-invasive strategy, combining clinical, biological and imaging data. The mainstay of the treatment remains venesection therapy with the perspective of hepcidin supplementation for hepcidin deprivation-related HC. Prevention of HC is critical at the family level and, for type 1 HC, remains a major goal, although still debated, at the population level., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
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19. Musculoskeletal Involvement in Hereditary Hemochromatosis.
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Castellanos-Moreira R, Rodríguez-García SC, Florez H, Inciarte-Mundo J, and Sanmarti R
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- Aged, Humans, Male, Metacarpophalangeal Joint diagnostic imaging, Metacarpophalangeal Joint pathology, Osteoarthritis diagnosis, Osteoarthritis etiology, Osteoarthritis physiopathology, Phlebotomy methods, Radiography methods, Bone Cysts diagnostic imaging, Chondrocalcinosis diagnosis, Chondrocalcinosis etiology, Chondrocalcinosis physiopathology, Hemochromatosis complications, Hemochromatosis diagnosis, Hemochromatosis physiopathology, Hemochromatosis therapy, Talus diagnostic imaging
- Published
- 2017
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20. Pathophysiological consequences and benefits of HFE mutations: 20 years of research.
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Hollerer I, Bachmann A, and Muckenthaler MU
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- Alzheimer Disease genetics, Alzheimer Disease metabolism, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis metabolism, Atherosclerosis genetics, Atherosclerosis metabolism, Hemochromatosis metabolism, Hemochromatosis physiopathology, Humans, Iron metabolism, Parkinson Disease genetics, Parkinson Disease metabolism, Genetic Predisposition to Disease genetics, Hemochromatosis genetics, Hemochromatosis Protein genetics, Mutation
- Abstract
Mutations in the HFE (hemochromatosis) gene cause hereditary hemochromatosis, an iron overload disorder that is hallmarked by excessive accumulation of iron in parenchymal organs. The HFE mutation p.Cys282Tyr is pathologically most relevant and occurs in the Caucasian population with a carrier frequency of up to 1 in 8 in specific European regions. Despite this high prevalence, the mutation causes a clinically relevant phenotype only in a minority of cases. In this review, we summarize historical facts and recent research findings about hereditary hemochromatosis, and outline the pathological consequences of the associated gene defects. In addition, we discuss potential advantages of HFE mutations in asymptomatic carriers., (Copyright© Ferrata Storti Foundation.)
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- 2017
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21. Hereditary haemochromatosis through 150 years.
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Ulvik RJ
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- Ferritins history, Ferritins metabolism, History, 19th Century, History, 20th Century, Humans, Medical Illustration history, Phlebotomy history, Transferrin history, Transferrin metabolism, Hemochromatosis genetics, Hemochromatosis history, Hemochromatosis physiopathology, Hemochromatosis therapy
- Published
- 2016
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22. Successful Treatment of Iron-Overload Cardiomyopathy in Hereditary Hemochromatosis With Deferoxamine and Deferiprone.
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Tauchenová L, Křížová B, Kubánek M, Fraňková S, Melenovský V, Tintěra J, Kautznerová D, Malušková J, Jirsa M, and Kautzner J
- Subjects
- Deferiprone, Ferritins analysis, Hemochromatosis Protein genetics, Humans, Iron Chelating Agents administration & dosage, Iron Overload blood, Iron Overload complications, Liver Diseases diagnosis, Liver Diseases etiology, Magnetic Resonance Imaging, Cine methods, Male, Middle Aged, Severity of Illness Index, Stroke Volume, Transferrin analysis, Treatment Outcome, Ventricular Dysfunction, Left diagnosis, Ventricular Dysfunction, Left etiology, Cardiomyopathies diagnosis, Cardiomyopathies etiology, Cardiomyopathies physiopathology, Cardiomyopathies therapy, Deferoxamine administration & dosage, Heart Failure diagnosis, Heart Failure drug therapy, Heart Failure etiology, Hemochromatosis blood, Hemochromatosis diagnosis, Hemochromatosis drug therapy, Hemochromatosis physiopathology, Pyridones administration & dosage
- Abstract
There is scarce evidence regarding the use of iron chelators in patients with hereditary hemochromatosis who are intolerant of phlebotomy or erythrocytapheresis. A 52-year-old man with genetically confirmed HFE hemochromatosis presented with liver disease and heart failure with severe left ventricular systolic dysfunction. Because of anemia after initial treatment, we added intravenous deferoxamine followed by oral deferiprone to less frequent erythrocytapheresis, which normalized systolic function within 1 year. Repeated cardiac magnetic resonance imaging revealed improvement of the T2* relaxation time. This report illustrates the beneficial effect of iron chelators in individuals with HFE hemochromatosis and poor tolerance of erythrocytapheresis., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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23. Haemochromatosis.
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Powell LW, Seckington RC, and Deugnier Y
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- Cation Transport Proteins genetics, Disease Management, Environmental Exposure, Europe epidemiology, Ferritins blood, Genotype, Hemochromatosis Protein, Histocompatibility Antigens Class I genetics, Humans, Liver drug effects, Liver Diseases etiology, Liver Diseases physiopathology, Liver Diseases therapy, Mass Screening methods, Mass Screening standards, Membrane Proteins genetics, Phenotype, Polymorphism, Single Nucleotide, Receptors, Transferrin genetics, Risk Factors, Sex Factors, Uncertainty, White People genetics, Alcohol Drinking adverse effects, Genetic Testing, Hemochromatosis diagnosis, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis therapy, Hepcidins deficiency, Iron metabolism, Liver metabolism, Mutation, Phlebotomy
- Abstract
Haemochromatosis is now known to be an iron-storage disease with genetic heterogeneity but with a final common metabolic pathway resulting in inappropriately low production of the hormone hepcidin. This leads to increase in intestinal absorption and deposition of excessive amounts of iron in parenchymal cells which in turn results in eventual tissue damage and organ failure. A clinical enigma has been the variable clinical expression with some patients presenting with hepatic cirrhosis at a young age and others almost asymptomatic for life. Research is unravelling this puzzle by identifying environmental factors-especially alcohol consumption-and associated modifying genes that modulate phenotypic expression. A high index of suspicion is required for early diagnosis but this can lead to presymptomatic therapy and a normal life expectancy. Venesection (phlebotomy) therapy remains the mainstay of therapy, but alternative therapies are the subject of current research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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24. Hereditary haemochromatosis.
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Mohamed M and Phillips J
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- Adult, Diagnosis, Differential, Ferritins blood, Humans, Iron Overload diagnosis, Iron Overload genetics, Liver Function Tests methods, Male, Mutation, Prognosis, Symptom Assessment methods, Transferrin analysis, Diagnostic Errors prevention & control, Hemochromatosis diagnosis, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis therapy, Hemochromatosis Protein genetics, Liver diagnostic imaging, Liver pathology, Phlebotomy methods
- Published
- 2016
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25. The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.
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Wallace DF and Subramaniam VN
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- Black People genetics, Female, Gene Frequency, Genetic Association Studies, Genotype, Hemochromatosis physiopathology, Hemochromatosis Protein genetics, High-Throughput Nucleotide Sequencing, Humans, Iron Overload genetics, Iron Overload pathology, Male, Mutation, Cation Transport Proteins genetics, GPI-Linked Proteins genetics, Hemochromatosis genetics, Hepcidins genetics, Receptors, Transferrin genetics
- Abstract
Purpose: The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH., Methods: A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined., Results: Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans., Conclusion: We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.Genet Med 18 6, 618-626.
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- 2016
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26. Hereditary hemochromatosis: Dealing with iron overload.
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Quigley P
- Subjects
- Hemochromatosis physiopathology, Humans, Male, Middle Aged, Nurse-Patient Relations, Nursing Diagnosis, Patient Education as Topic, Hemochromatosis genetics, Hemochromatosis nursing, Iron Overload nursing
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- 2016
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27. HFE-Related Hereditary Hemochromatosis Is Not Invariably a Disease of Adulthood: Importance of Early Diagnosis and Phlebotomy in Childhood.
- Author
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Islek A, Inci A, Sayar E, Yilmaz A, Uzun OC, and Artan R
- Subjects
- Age of Onset, Amino Acid Substitution, Child, Diagnosis, Differential, Early Diagnosis, Growth Disorders etiology, Growth Disorders prevention & control, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis surgery, Hemochromatosis Protein genetics, Heterozygote, Humans, Male, Mutation, Phlebotomy, Treatment Outcome, Turkey, Twins, Asymptomatic Diseases, Hemochromatosis diagnosis
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- 2016
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28. Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study.
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Seravalle G, Piperno A, Mariani R, Pelloni I, Facchetti R, Dell'Oro R, Cuspidi C, Mancia G, and Grassi G
- Subjects
- Adrenocortical Hyperfunction physiopathology, Adult, Baroreflex drug effects, Blood Pressure drug effects, Case-Control Studies, Ferritins metabolism, Heart Rate drug effects, Hemochromatosis drug therapy, Hemochromatosis genetics, Humans, Iron Chelating Agents therapeutic use, Iron Overload drug therapy, Iron Overload physiopathology, Male, Muscle, Skeletal innervation, Transferrin metabolism, Hemochromatosis physiopathology, Sympathetic Nervous System physiology
- Abstract
Aims: Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown., Methods and Results: In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation., Conclusion: These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)
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- 2016
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29. Decreasing iron-related indexes without anaemia in a patient with genetic haemochromatosis.
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Conti CB, Baccarin A, Conte D, and Fraquelli M
- Subjects
- Anemia complications, Anemia diagnosis, Hemochromatosis physiopathology, Humans, Male, Middle Aged, Anemia etiology, Hemochromatosis genetics, Iron metabolism
- Abstract
Present case report refers to a 48-year-old man with genetic haemochromatosis (C282Y mut/mut) diagnosed at the age of 26. After aggressive iron depleting regimen carried out up to normalization of iron-related indexes, he received a maintenance regimen based on regular phlebotomies for about 20 years. In 2014, a marked reduction of both serum ferritin and transferrin saturation percent, without concomitant anaemia, was noted on two different occasions at 5-month interval. An obscure occult GI bleeding was suspected, but both upper and lower GI tract endoscopy were negative for abnormal findings, as also was a detailed abdominal US scan. The persistence of low iron-related indexes prompted the physicians to perform a videocapsule endoscopy, which showed an ulcerative bleeding lesion in the small bowel, not confirmed however by both anterograde and retrograde double-balloon enteroscopy. Further MRI and PET allowed the identification of a 3.5 cm large lesion, located outside the small bowel wall, suspected to be a gastrointestinal stromal tumour (GIST). A further laparoscopic procedure allowed the resection of 10 cm of midileum, which included the mass, fully consistent with GIST at pathology.
- Published
- 2015
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30. Adipocyte iron regulates leptin and food intake.
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Gao Y, Li Z, Gabrielsen JS, Simcox JA, Lee SH, Jones D, Cooksey B, Stoddard G, Cefalu WT, and McClain DA
- Subjects
- 3T3-L1 Cells, Animals, Cyclic AMP Response Element-Binding Protein genetics, Cyclic AMP Response Element-Binding Protein metabolism, Eating genetics, Ferritins metabolism, Gene Expression Regulation drug effects, Hemochromatosis genetics, Hemochromatosis mortality, Hemochromatosis physiopathology, Mice, Mice, Mutant Strains, Response Elements, Adipocytes metabolism, Dietary Supplements, Eating drug effects, Hemochromatosis metabolism, Iron metabolism, Iron pharmacology, Leptin metabolism
- Abstract
Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression.
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- 2015
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31. A 42-year-old man with elevated ferritin.
- Author
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Lanktree MB, Sadikovic B, and Crowther MA
- Subjects
- Adult, Arthralgia diagnosis, Arthralgia etiology, Blood Chemical Analysis, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 drug therapy, Fatigue diagnosis, Fatigue etiology, Follow-Up Studies, Hemochromatosis physiopathology, Humans, Male, Metformin therapeutic use, Risk Assessment, Treatment Outcome, Ferritins blood, Hemochromatosis blood, Hemochromatosis therapy, Phlebotomy methods
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- 2015
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32. Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a GNPAT variant associated with severe iron overload.
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McLaren CE, Emond MJ, Subramaniam VN, Phatak PD, Barton JC, Adams PC, Goh JB, McDonald CJ, Powell LW, Gurrin LC, Allen KJ, Nickerson DA, Louie T, Ramm GA, Anderson GJ, and McLaren GD
- Subjects
- Alleles, Analysis of Variance, Blotting, Western, Case-Control Studies, Exome genetics, Exome physiology, Ferritins blood, Hemochromatosis physiopathology, Hemochromatosis Protein, Hep G2 Cells, Homozygote, Humans, Iron Overload physiopathology, Liver Cirrhosis genetics, Liver Cirrhosis physiopathology, Male, Phenotype, Point Mutation, RNA, Small Interfering genetics, Real-Time Polymerase Chain Reaction methods, Sequence Analysis, Protein, Severity of Illness Index, Acyltransferases genetics, Genetic Variation, Hemochromatosis genetics, Histocompatibility Antigens Class I genetics, Iron Overload genetics, Membrane Proteins genetics
- Abstract
Unlabelled: To identify polymorphisms associated with variability of iron overload severity in HFE-associated hemochromatosis, we performed exome sequencing of DNA from 35 male HFE C282Y homozygotes with either markedly increased iron stores (n = 22; cases) or with normal or mildly increased iron stores (n = 13; controls). The 35 participants, residents of the United States, Canada, and Australia, reported no or light alcohol consumption. Sequencing data included 82,068 single-nucleotide variants, and 10,337 genes were tested for a difference between cases and controls. A variant in the GNPAT gene showed the most significant association with severe iron overload (P = 3 × 10(-6) ; P = 0.033 by the likelihood ratio test after correction for multiple comparisons). Sixteen of twenty-two participants with severe iron overload had glyceronephosphate O-acyltransferase (GNPAT) polymorphism p.D519G (rs11558492; 15 heterozygotes, one homozygote). No control participant had this polymorphism. To examine functional consequences of GNPAT deficiency, we performed small interfering RNA-based knockdown of GNPAT in the human liver-derived cell line, HepG2/C3A. This knockdown resulted in a >17-fold decrease in expression of the messenger RNA encoding the iron-regulatory hormone, hepcidin., Conclusion: GNPAT p.D519G is associated with a high-iron phenotype in HFE C282Y homozygotes and may participate in hepcidin regulation., (© 2015 by the American Association for the Study of Liver Diseases.)
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- 2015
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33. Liver transplantation for neonatal hemochromatosis: analysis of the UNOS database.
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Sheflin-Findling S, Annunziato RA, Chu J, Arvelakis A, Mahon D, and Arnon R
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- Female, Graft Rejection surgery, Graft Survival, Hemochromatosis physiopathology, Humans, Infant, Newborn, Liver Failure, Acute surgery, Male, Risk Factors, Treatment Outcome, United States, Waiting Lists, Databases, Factual, Hemochromatosis surgery, Liver Transplantation
- Abstract
NH is the most common identifiable cause of ALF in the neonate. LT is the definitive treatment for neonates with NH who have failed medical therapy. Our aim was to determine the outcomes of LT in infants with NH. Patients (less than one yr of age) with NH who were listed for LT and patients who underwent LT between 1994 and 2013 were identified from the UNOS database for analysis. Risk factors for death and graft loss were analyzed by multivariate logistic regression. Thirty-eight infants with NH with a total of 43 transplants were identified. One- and five-yr patient and graft survival were 84.2%, 81.6%, 71.1%, and 68.4%, respectively. The outcomes for NH were not significantly different when compared to the same age-matched recipients with other causes of ALF. There were no statistically significant risk factors identified for graft loss or death. Ninety infants with NH were listed for LT. Reasons for removal included transplanted (49%), death (27%), too sick to transplant (7%), and improved status (13%). LT for infants with NH has a high rate of graft loss and death; however, outcomes are comparable to the same age-matched recipients with other causes of ALF., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2015
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34. Adult liver disorders caused by inborn errors of metabolism: review and update.
- Author
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Chanprasert S and Scaglia F
- Subjects
- Adult, Calcium-Binding Proteins deficiency, Child, Hemochromatosis diagnosis, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis therapy, Hemochromatosis Protein, Hepatolenticular Degeneration diagnosis, Hepatolenticular Degeneration genetics, Hepatolenticular Degeneration physiopathology, Histocompatibility Antigens Class I genetics, Humans, Membrane Proteins genetics, Organic Anion Transporters deficiency, alpha 1-Antitrypsin Deficiency diagnosis, alpha 1-Antitrypsin Deficiency genetics, alpha 1-Antitrypsin Deficiency physiopathology, alpha 1-Antitrypsin Deficiency therapy, Liver Diseases diagnosis, Liver Diseases physiopathology, Metabolism, Inborn Errors diagnosis, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors physiopathology, Metabolism, Inborn Errors therapy
- Abstract
Inborn errors of metabolism (IEMs) are a group of genetic diseases that have protean clinical manifestations and can involve several organ systems. The age of onset is highly variable but IEMs afflict mostly the pediatric population. However, in the past decades, the advancement in management and new therapeutic approaches have led to the improvement in IEM patient care. As a result, many patients with IEMs are surviving into adulthood and developing their own set of complications. In addition, some IEMs will present in adulthood. It is important for internists to have the knowledge and be familiar with these conditions because it is predicted that more and more adult patients with IEMs will need continuity of care in the near future. The review will focus on Wilson disease, alpha-1 antitrypsin deficiency, citrin deficiency, and HFE-associated hemochromatosis which are typically found in the adult population. Clinical manifestations and pathophysiology, particularly those that relate to hepatic disease as well as diagnosis and management will be discussed in detail., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
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35. Mechanistic and regulatory aspects of intestinal iron absorption.
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Gulec S, Anderson GJ, and Collins JF
- Subjects
- Anemia, Iron-Deficiency physiopathology, Animals, Biological Availability, Cation Transport Proteins genetics, Cation Transport Proteins metabolism, Cytochromes b metabolism, Diet, Enterocytes metabolism, Ferric Compounds metabolism, Heme metabolism, Hemochromatosis physiopathology, Hepatocytes metabolism, Hepcidins physiology, Homeostasis physiology, Humans, Microvilli metabolism, Intestinal Absorption physiology, Iron metabolism
- Abstract
Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands., (Copyright © 2014 the American Physiological Society.)
- Published
- 2014
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36. The efficiency of therapeutic erythrocytapheresis compared to phlebotomy: a mathematical tool for predicting response in hereditary hemochromatosis, polycythemia vera, and secondary erythrocytosis.
- Author
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Evers D, Kerkhoffs JL, Van Egmond L, Schipperus MR, and Wijermans PW
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Volume, Cytapheresis statistics & numerical data, Female, Hematocrit, Hemochromatosis blood, Hemochromatosis physiopathology, Humans, Male, Mathematical Concepts, Middle Aged, Models, Theoretical, Phlebotomy statistics & numerical data, Polycythemia blood, Polycythemia physiopathology, Polycythemia Vera blood, Polycythemia Vera physiopathology, Retrospective Studies, Treatment Outcome, Young Adult, Cytapheresis methods, Hemochromatosis therapy, Phlebotomy methods, Polycythemia therapy, Polycythemia Vera therapy
- Abstract
Recently, therapeutic erythrocytapheresis (TE) was suggested to be more efficient in depletion of red blood cells (RBC) compared to manual phlebotomy in the treatment of hereditary hemochromatosis (HH), polycythemia vera (PV), and secondary erythrocytosis (SE). The efficiency rate (ER) of TE, that is, the increase in RBC depletion achieved with one TE cycle compared to one phlebotomy procedure, can be calculated based on estimated blood volume (BV), preprocedural hematocrit (Hct(B)), and delta-hematocrit (ΔHct). In a retrospective evaluation of 843 TE procedures (in 45 HH, 33 PV, and 40 SE patients) the mean ER was 1.86 ± 0.62 with the highest rates achieved in HH patients. An ER of 1.5 was not reached in 37.9% of all procedures mainly concerning patients with a BV below 4,500 ml. In 12 newly diagnosed homozygous HH patients, the induction phase duration was medially 38.4 weeks (medially 10.5 procedures). During the maintenance treatment of HH, PV, and SE, the interval between TE procedures was medially 13.4 weeks. This mathematical model can help select the proper treatment modality for the individual patient. Especially for patients with a large BV and high achievable ΔHct, TE appears to be more efficient than manual phlebotomy in RBC depletion thereby potentially reducing the numbers of procedures and expanding the interprocedural time period for HH, PV, and SE., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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37. Disordered vascular compliance in haemochromatosis.
- Author
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Cash WJ, O'Neill S, O'Donnell ME, McCance DR, Young IS, McEneny J, Cadden IS, McDougall NI, and Callender ME
- Subjects
- Adult, Aged, Ascorbic Acid blood, Biomarkers blood, Blood Pressure physiology, C-Reactive Protein analysis, Case-Control Studies, Cell Adhesion Molecules blood, Compliance physiology, Female, Hemochromatosis genetics, Homozygote, Humans, Lipid Peroxides blood, Male, Middle Aged, Pulse Wave Analysis, Risk Factors, Sex Factors, Vitamin A blood, gamma-Tocopherol blood, Endothelium, Vascular physiopathology, Hemochromatosis physiopathology
- Abstract
Background: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk., Aims: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls., Methods: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured., Results: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 μmol/L, p = 0.011), retinol (1.17 vs. 1.81 μmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 μmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32)., Conclusions: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.
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- 2014
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38. Endoscopic and histologic abnormalities of gastrointestinal tract in patients with hereditary hemochromatosis.
- Author
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Zhou WX, Wu XR, Bennett AE, and Shen B
- Subjects
- Aged, Biopsy, Colonoscopy, Endoscopy, Digestive System, Female, Gastrointestinal Diseases epidemiology, Gastrointestinal Diseases physiopathology, Hemochromatosis physiopathology, Humans, Inflammation epidemiology, Inflammation physiopathology, Male, Middle Aged, Gastrointestinal Diseases etiology, Gastrointestinal Tract physiopathology, Hemochromatosis complications, Inflammation etiology
- Abstract
Background: Patients with iron overload frequently complained of upper gastrointestinal (GI) symptoms. This study aimed to systemically evaluate the association between hereditary hemochromatosis (HH) and gut inflammation., Patients and Methods: HH patients were identified using the ICD-9 codes. Inclusion criteria were patients with primary HH who had esophagogastroduodenoscopy (EGD) and/or colonoscopy with GI biopsies (N=39). Patients undergoing EGD with duodenal biopsy for the indication of "rule out celiac disease" were included in the control group (N=40). GI biopsy specimens were rereviewed and scored., Results: Of the 39 patients with genetically confirmed primary HH in the study group, 28 (71.8%) had liver biopsy and 25 (89.3%) of them showed iron deposition. Twenty-five patients (64.1%) had EGD and 23 (59.0%) had colonoscopy. Histologic inflammation was identified in the esophagus in 2 patients (8.0%), stomach in 11 (44.0%), duodenum in 2 (8.7%), and colon in 3 (13.0%). Duodenal biopsy specimen was available for rereview in 16 patients (41.0%). Patient demographics were comparable between the 16 cases in the study group and the 40 cases in the control group. On histology, the frequency of intraepithelial lymphocytosis of small intestine was 25.5% in the HH cases versus 2.5% in controls (P=0.020). HH patients also had a greater proportion of intraepithelial neutrophil infiltration (31.2% vs. 2.5%, P=0.006) and lamina propria lymphocyte infiltration (31.2% vs. 0%, P=0.001) than controls., Conclusions: GI inflammation was common in HH patients, which from the different perspective, supports the notion that iron overload may lead to GI inflammation.
- Published
- 2014
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39. Non-HFE hemochromatosis: pathophysiological and diagnostic aspects.
- Author
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Bardou-Jacquet E, Ben Ali Z, Beaumont-Epinette MP, Loreal O, Jouanolle AM, and Brissot P
- Subjects
- Alcohol Drinking physiopathology, Benzoates therapeutic use, Biopsy, Cataract congenital, Cataract physiopathology, Cation Transport Proteins genetics, Decision Trees, Deferasirox, Diet, Gaucher Disease physiopathology, Genetic Testing, Hemochromatosis etiology, Hemochromatosis therapy, Hemochromatosis Protein, Hepcidins deficiency, Hepcidins physiology, Histocompatibility Antigens Class I genetics, Humans, Inflammation physiopathology, Iron metabolism, Iron Chelating Agents therapeutic use, Iron Metabolism Disorders congenital, Iron Metabolism Disorders physiopathology, Iron Overload physiopathology, Liver injuries, Liver pathology, Macrophage Activation Syndrome physiopathology, Magnetic Resonance Imaging, Membrane Proteins genetics, Metabolic Syndrome physiopathology, Mutation, Phlebotomy, Receptors, Transferrin genetics, Transferrin analysis, Triazoles therapeutic use, Hemochromatosis diagnosis, Hemochromatosis physiopathology
- Abstract
Rare genetic iron overload diseases are an evolving field due to major advances in genetics and molecular biology. Genetic iron overload has long been confined to the classical type 1 hemochromatosis related to the HFE C282Y mutation. Breakthroughs in the understanding of iron metabolism biology and molecular mechanisms led to the discovery of new genes and subsequently, new types of hemochromatosis. To date, four types of hemochromatosis have been identified: HFE-related or type1 hemochromatosis, the most frequent form in Caucasians, and four rare types, named type 2 (A and B) hemochromatosis (juvenile hemochromatosis due to hemojuvelin and hepcidin mutation), type 3 hemochromatosis (related to transferrin receptor 2 mutation), and type 4 (A and B) hemochromatosis (ferroportin disease). The diagnosis relies on the comprehension of the involved physiological defect that can now be explored by biological and imaging tools, which allow non-invasive assessment of iron metabolism. A multidisciplinary approach is essential to support the physicians in the diagnosis and management of those rare diseases., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
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40. Endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes.
- Author
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Cash WJ, O'Neill S, O'Donnell ME, McCance DR, Young IS, McEneny J, McDougall NI, and Callender ME
- Subjects
- Adult, Aged, Biomarkers metabolism, C-Reactive Protein metabolism, Female, Follow-Up Studies, Homozygote, Humans, Lipid Peroxides metabolism, Male, Middle Aged, Neoplasm Grading, Pilot Projects, Prognosis, Pulse Wave Analysis, Young Adult, Antioxidants metabolism, Blood Vessels physiopathology, Endothelium, Vascular physiopathology, Hemochromatosis physiopathology
- Abstract
Purpose: This pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection., Patients/methods: Untreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies., Results: Ten patients were recruited (M=8, F=2, mean age=51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p=0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 μmol/L vs. 0.51 μmol/L, p=0.45, 427.4 ng/ml vs. 307.22 ng/ml, p=0.54, 517.70 ng/ml vs. 377.50 ng/ml, p=0.51 and 290.75 μg/dL vs. 224.26 μg/dL, p=0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p=0.34)., Conclusions: Venesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)
- Published
- 2014
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41. Cardiac involvement in hemochromatosis.
- Author
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Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, and Frishman WH
- Subjects
- Biopsy, Heart Failure mortality, Hemochromatosis therapy, Humans, Iron metabolism, Iron Chelating Agents therapeutic use, Liver pathology, Phlebotomy, Survival Rate, Treatment Outcome, Heart physiopathology, Heart Failure etiology, Heart Failure physiopathology, Hemochromatosis complications, Hemochromatosis physiopathology
- Abstract
Cardiac hemochromatosis or primary iron-overload cardiomyopathy is an important and potentially preventable cause of heart failure. This is initially characterized by diastolic dysfunction and arrhythmias and in later stages by dilated cardiomyopathy. Diagnosis of iron overload is established by elevated transferrin saturation (>55%) and elevated serum ferritin (>300 ng/mL). Genetic testing for mutations in the HFE (high iron) gene and other proteins, such as hemojuvelin, transferrin receptor, and ferroportin, should be performed if secondary causes of iron overload are ruled out. Patients should undergo comprehensive 2D and Doppler echocardiography to evaluate their systolic and diastolic function. Newer modalities like strain imaging and speckle-tracking echocardiography hold promise for earlier detection of cardiac involvement. Cardiac magnetic resonance imaging with measurement of T2* relaxation times can help quantify myocardial iron overload. In addition to its value in diagnosis of cardiac iron overload, response to iron reduction therapy can be assessed by serial imaging. Therapeutic phlebotomy and iron chelation are the cornerstones of therapy. The average survival is less than a year in untreated patients with severe cardiac impairment. However, if treated early and aggressively, the survival rate approaches that of the regular heart failure population.
- Published
- 2014
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42. Diabetes and hemochromatosis.
- Author
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Creighton Mitchell T and McClain DA
- Subjects
- Cardiovascular Diseases physiopathology, Diabetes Mellitus, Type 2 physiopathology, Female, Genetic Predisposition to Disease, Genotype, Hemochromatosis physiopathology, Humans, Male, Mass Screening, Prevalence, Cardiovascular Diseases metabolism, Diabetes Mellitus, Type 2 metabolism, Ferritins metabolism, Hemochromatosis metabolism, Phlebotomy methods
- Abstract
The common form of hereditary hemochromatosis is an autosomal recessive disorder most prevalent in Caucasians that results in excessive iron storage. The clinical manifestations of hemochromatosis are protean. HFE genotype, which determines the degree of iron overload and duration of disease have profound effects on disease expression. The prevalence of diabetes in this population has likely been underestimated because of studies that include a broad range of ethnicities and associating diabetes with allele frequency in spite of the decreased risk of diabetes in heterozygotes compared with homozygotes. Loss of insulin secretory capacity is likely the primary defect contributing to development of diabetes with insulin resistance playing a secondary role. Phlebotomy can ameliorate the defects in insulin secretion if initiated early. Screening a select population of individuals with type 2 diabetes may identify patients with hemochromatosis early and substantially impact individual clinical outcomes.
- Published
- 2014
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43. Iron metabolism: bedside to bench and back.
- Author
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Means RT Jr
- Subjects
- Anemia physiopathology, Anemia therapy, Animals, Disease Management, Disease Models, Animal, Hemochromatosis physiopathology, Hemochromatosis therapy, Humans, Iron Metabolism Disorders metabolism, Hepcidins physiology, Iron metabolism, Iron Metabolism Disorders physiopathology, Iron Metabolism Disorders therapy
- Published
- 2013
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44. Hemochromatosis and iron overload: from bench to clinic.
- Author
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Barton JC
- Subjects
- Hemochromatosis history, Hemochromatosis therapy, Hemochromatosis Protein, Hepcidins physiology, Histocompatibility Antigens Class I physiology, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, Homeostasis physiology, Humans, Iron Overload history, Iron Overload therapy, Membrane Proteins physiology, Hemochromatosis physiopathology, Iron metabolism, Iron Overload physiopathology
- Published
- 2013
- Full Text
- View/download PDF
45. The iron reabsorption index: a new phenotypic and pathophysiological descriptor in HFE hemochromatosis.
- Author
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Manet G, Bardou-Jacquet E, Perrin M, Morcet J, Sinteff JP, Lainé F, Moirand R, and Deugnier Y
- Subjects
- Adolescent, Adult, Aged, Amino Acid Substitution, Cohort Studies, Female, Ferritins blood, Follow-Up Studies, Hemochromatosis genetics, Hemochromatosis physiopathology, Hemochromatosis therapy, Hemochromatosis Protein, Hemoglobins metabolism, Histocompatibility Antigens Class I genetics, Humans, Male, Membrane Proteins genetics, Middle Aged, Phenotype, Phlebotomy, Young Adult, Hemochromatosis blood, Iron blood
- Abstract
Background: The current phenotypic descriptors of high Fe gene hemochromatosis are hardly specific and time dependent in a context of highly variable expressivity. We hypothesized that the rate of iron removed during maintenance therapy and corresponding to the iron reabsorption index (IRI) could be patient specific and may then represent a new useful phenotypic marker., Aim: The present study aimed to describe IRI with respect to its phenotypic specificity and to its potential usefulness., Methods: We studied a cohort of 316 p.Cys282Tyr homozygous patients with stable low serum ferritin levels on maintenance therapy for at least 12 months. Characteristics at diagnosis, date and volume of phlebotomies, and parameters of iron metabolism throughout maintenance therapy were determined., Results: IRI ranged from 1.3 to 6.1 mg/day (median: 2.44). It was lower in women (difference: 1.26 mg/day), mainly explained by physiological blood loss, weight, and alcohol consumption. IRI was correlated to iron burden and fibrosis stage at diagnosis, was stable over time (variation: 11.5%), and depended on serum ferritin level during therapy., Conclusion: Its independence from disease duration, its stability, its wide distribution, and its significant correlation with iron burden markers make IRI a valuable potential phenotypic indicator of the daily iron overabsorption in hemochromatosis. Moreover, IRI provides a conceptual frame for empiric adaptation of maintenance therapy.
- Published
- 2013
- Full Text
- View/download PDF
46. The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions.
- Author
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Mastrogiannaki M, Matak P, and Peyssonnaux C
- Subjects
- Animals, Antimicrobial Cationic Peptides metabolism, Enterocytes cytology, Hemochromatosis metabolism, Hemochromatosis physiopathology, Hepatocytes metabolism, Hepcidins, Homeostasis, Humans, Hypoxia, Inflammation metabolism, Inflammation physiopathology, Iron Regulatory Protein 1 metabolism, Iron Regulatory Protein 2 metabolism, Male, Mice, Polycythemia metabolism, Polycythemia physiopathology, Basic Helix-Loop-Helix Transcription Factors metabolism, Gastrointestinal Tract metabolism, Gastrointestinal Tract physiopathology, Gene Expression Regulation, Iron metabolism
- Abstract
Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2-based therapeutic strategies in iron-related pathological conditions.
- Published
- 2013
- Full Text
- View/download PDF
47. Absorption of manganese and iron in a mouse model of hemochromatosis.
- Author
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Kim J, Buckett PD, and Wessling-Resnick M
- Subjects
- Animals, Blood Circulation, Cation Transport Proteins metabolism, Disease Models, Animal, Hemochromatosis physiopathology, Hemochromatosis Protein, Histocompatibility Antigens Class I metabolism, Injections, Intravenous, Iron administration & dosage, Male, Manganese administration & dosage, Membrane Proteins deficiency, Membrane Proteins metabolism, Mice, Mice, Knockout, Olfactory Bulb metabolism, Organ Specificity, Hemochromatosis metabolism, Intestinal Absorption, Iron metabolism, Manganese metabolism
- Abstract
Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal iron absorption, is commonly caused by loss of HFE gene function. Both iron and manganese absorption are regulated by iron status, but the relationships between the transport pathways of these metals and how they are affected by HFE-associated hemochromatosis remain poorly understood. Loss of HFE function is known to alter the intestinal expression of DMT1 (divalent metal transporter-1) and Fpn (ferroportin), transporters that have been implicated in absorption of both iron and manganese. Although the influence of HFE deficiency on dietary iron absorption has been characterized, potential effects on manganese metabolism have yet to be explored. To investigate the role of HFE in manganese absorption, we characterized the uptake and distribution of the metal in Hfe (-/-) knockout mice after intravenous, intragastric, and intranasal administration of (54)Mn. These values were compared to intravenous and intragastric administration of (59)Fe. Intestinal absorption of (59)Fe was increased and clearance of injected (59)Fe was also increased in Hfe(-/-) mice compared to controls. Hfe (-/-) mice displayed greater intestinal absorption of (54)Mn compared to wild-type Hfe(+/+) control mice. After intravenous injection, the distribution of (59)Fe to heart and liver was greater in Hfe (-/-) mice but no remarkable differences were observed for (54)Mn. Although olfactory absorption of (54)Mn into blood was unchanged in Hfe (-/-) mice, higher levels of intranasally-instilled (54)Mn were associated with Hfe(-/-) brain compared to controls. These results show that manganese transport and metabolism can be modified by HFE deficiency.
- Published
- 2013
- Full Text
- View/download PDF
48. Idiopathic hand osteoarthritis vs haemochromatosis arthropathy--a clinical, functional and radiographic study.
- Author
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Dallos T, Sahinbegovic E, Stamm T, Aigner E, Axmann R, Stadlmayr A, Englbrecht M, Datz C, Schett G, and Zwerina J
- Subjects
- Aged, Arthralgia diagnostic imaging, Arthralgia physiopathology, Cohort Studies, Cross-Sectional Studies, Female, Hand Joints physiopathology, Hemochromatosis epidemiology, Hemochromatosis physiopathology, Humans, Incidence, Male, Middle Aged, Osteoarthritis epidemiology, Osteoarthritis physiopathology, Prognosis, Prospective Studies, Radiography, Risk Assessment, Severity of Illness Index, Hand Joints diagnostic imaging, Hemochromatosis diagnostic imaging, Osteoarthritis diagnostic imaging, Pain Measurement, Range of Motion, Articular physiology
- Abstract
Objective: Haemochromatosis arthropathy is a secondary OA and the most frequent and earliest clinical presentation of hereditary haemochromatosis (HH). The aim of this study was to perform a direct clinical, functional and radiographic comparison with idiopathic hand OA (HOA) to unravel important differences between these clinical entities., Methods: In total, 299 patients (141 with HH arthropathy of the hands and 158 patients with idiopathic HOA) were recruited. Structured clinical assessment including hand function tests, as well as hand radiographs with scoring according to Kellgren-Lawrence, were carried out in all patients., Results: HH arthropathy and HOA differed significantly: patients with HH arthropathy were younger and predominantly male as compared with HOA. In males but not females, HH arthropathy led to an earlier start of symptoms than in HOA. Patients with HOA had more tender joints and worse hand function than patients with HH arthropathy, although subjective measures of joint pain and function were similar. MCP and wrist joint involvement was more frequent and severe in HH arthropathy, while HOA patients more frequently had degenerative changes in the first CMC as well as PIP and DIP joints., Conclusion: HH arthropathy and idiopathic HOA differ significantly in terms of epidemiology, localization, severity of symptoms and radiographic changes.
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- 2013
- Full Text
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49. The efficiency of therapeutic erythrocytapheresis compared to phlebotomy in relation to blood volume and delta-hematocrit: an evaluation in hereditary hemochromatosis polycythemia vera and secondary erythrocytosis.
- Author
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Evers D, Kerkhoffs JL, Van Egmond L, and Wijermans PW
- Subjects
- Female, Hematocrit, Humans, Male, Blood Volume, Cytapheresis, Hemochromatosis physiopathology, Hemochromatosis therapy, Models, Biological, Phlebotomy, Polycythemia physiopathology, Polycythemia therapy, Polycythemia Vera physiopathology, Polycythemia Vera therapy
- Published
- 2013
- Full Text
- View/download PDF
50. Iron and diabetes risk.
- Author
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Simcox JA and McClain DA
- Subjects
- Adiponectin metabolism, Glucose metabolism, Hemochromatosis physiopathology, Humans, Iron, Dietary metabolism, Lipid Metabolism physiology, Diabetes Mellitus, Type 2 etiology, Homeostasis physiology, Insulin Resistance physiology, Insulin-Secreting Cells metabolism, Iron Overload complications, Iron, Dietary adverse effects, Models, Biological
- Abstract
Iron overload is a risk factor for diabetes. The link between iron and diabetes was first recognized in pathologic conditions-hereditary hemochromatosis and thalassemia-but high levels of dietary iron also impart diabetes risk. Iron plays a direct and causal role in diabetes pathogenesis mediated both by β cell failure and insulin resistance. Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role. The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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