DOCSLIB.ORG

EIC 2018 Abstract Book

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
EIC 2018 Abstract Book 2018 ABSTRACT BOOK EUROPEAN IRON CLUB ANNUAL MEETING 2018, ZÜRICH ORAL SESSIONS AND POSTERS ETH ZÜRICH | Rämistrasse 101, 8092 Zürich S ORAL SESSION ABSTRACTS Oral abstracts Feb 8 – Session 1 Biogenesis of iron-sulfur proteins in eukaryotes: An overview on components, mechanisms, and diseases Roland Lill, PhD Institut für Zytobiologie, Philipps-Universität Marburg – Germany E-mail: [email protected] Iron-sulfur (Fe/S) clusters are evolutionary ancient, inorganic cofactors of proteins with essential functions in catalysis, electron transfer and regulation. Synthesis of Fe/S clusters and their assembly into apoproteins in a living cell is a complex process involving more than 30 proteins in mitochondria and cytosol of eukaryotes (1- 4). Biogenesis of mitochondrial Fe/S proteins is accomplished by the iron-sulfur cluster (ISC) assembly machinery which was inherited from bacteria during evolution. Cytosolic and nuclear Fe/S protein assembly also depends on the function of this machinery, yet additionally requires the mitochondrial export apparatus and the cytosolic iron-sulfur protein assembly (CIA) machinery. While we have a good picture of the general outline of Fe/S protein biogenesis (Figure), the detailed molecular mechanisms underlying the individual reaction steps are only now being unraveled by biochemical, biophysical, bioinorganic and ultra-structural methods. The presentation will summarize new aspects concerning the basic mechanisms of cellular Fe/S protein maturation in yeast and human cells. I will also explain how functional impairment of the ISC components results in various “Fe/S diseases” with complex hematological, metabolic or neurodegenerative phenotypes [5]. References (Reviews) [1] Lill, R. (2009) Nature 460, 831-838. [2] Lill, R. et al. (2012) BBA 1823, 1491-1508; Braymer & Lill (2017) J. Biol. Chem. 292, 12754–63. [3] Netz, D.J., Mascarenhas, J., Stehling, O., Pierik, A.J., Lill, R. (2014) Trends Cell Biol 24, 303-312. [4] Paul, V.D. and Lill, R. (2015). BBA 1853, 1528-1539; and Cell Metab. 20, 384. [5] Stehling, O., Wilbrecht, C., & Lill, R. (2014). Biochimie 100, 61-77; and Stehling, O. & Lill, R. (2013). Cold Spring Harb Perspect Biol 5:a011312 1 Oral abstracts Feb 8 – Session 1 Systemic and cellular iron metabolism Martina U. Muckenthaler Department of Pediatrics, University of Heidelberg, Molecular Medicine Partnership Unit (EMBL), Heidelberg, Germany Imbalances of iron homeostasis account for some of the most common human diseases, whereby severe pathologies result from both iron deficiency and overload. At the cellular level iron homeostasis is maintained by the iron regulatory proteins (IRPs)-1 and -2 that posttranscriptionally control expression of proteins involved in iron uptake, storage and export. Interestingly, the IRE/IRP regulon extends beyond validated iron-related targets, suggesting links between iron metabolism and other physiological cellular processes. At the systemic level iron homeostasis is controlled by the hepcidin/ferroportin regulatory system. The small peptide hormone hepcidin orchestrates systemic iron fluxes and controls plasma iron levels by binding to the iron exporter ferroportin on the surface of iron releasing cell types, triggering its degradation and hence reducing iron transfer to transferrin. Hepcidin thus maintains transferrin saturation at physiological levels assuring adequate iron supplies to all cell types. My presentation will focus on regulatory mechanisms involved in maintaining iron homeostasis and the pathological consequences that arise if these systems are disrupted. 2 Oral abstracts Feb 8 – Session 1 The pioneering role of the Rennes school in haemochromatosis Pierre Brissot University of Rennes1 and Inserm-U 1241, Rennes, France This presentation is dedicated to the memory of Profs Michel Bourel and Marcel Simon who were the true Rennes pioneers in haemochromatosis (HC), to all colleagues and friends who got involved in this exciting adventure, and to all patients affected by this severe and still underdiagnosed disease. The Rennes studies have, over time, covered seven main domains: i) Contribution to the semiological description of HC. It concerned several aspects (dermatology, hepatology, endocrinology, rheumatology, and cardiology) ; ii) Refining new ways of investigating iron overload, among which ferritinemia, liver histology, liver iron concentration, and magnetic resonance imaging ; iii) Providing the first demonstration of the hereditary nature of the disease, based on the HLA approach ; iv) Emphasizing the importance of non-transferrin bound iron for explaining both cellular iron deposition and toxicity ; v) Demonstrating, for the first time, the role of hepcidin in iron metabolism ; vi) Refining the knowledge of non-HFE HC through the creation of the national reference center for rare genetic iron overload diseases ; vii) Giving patients their voice, via the creation of support structures at the regional, national (FFAMH, AHF), european (EFAPH) and global (HI) levels. 3 Oral abstracts Feb 8 – Session 1 Diagnosis of atypical iron overload disorders by next generation sequencing Domenico Girelli, MD PhD Department of Medicine, University of Verona Veneto Region Referral Center for Iron Metabolism Disorders, Policlinico G.B. Rossi, 37134 Verona Italy Atypical iron overload disorders (AIOD) are a heterogeneous group including a number of rare genetic diseases ranging from non-classical (or “non-HFE”) hereditary hemochromatosis (HH) to conditions in which iron accumulates at unusual sites, for example in the central nervous system. An accurate molecular diagnosis of these conditions has long been proven challenging. Traditionally, it required cumbersome and stepwise sequencing of candidate genes, prioritizing them on the basis of clinical clues (age of onset, ethnicity, phenotypic features fitting with current knowledge on HH subtypes). The advent of next-generation-sequencing (NGS) techniques is rapidly changing the scenario. Several Referral Centers are now able to perform targeted NGS allowing rapid and simultaneous analysis of gene panels, if not whole exome sequencing (WES) or whole genome sequencing (WGS). Costs are rapidly declining, potentially allowing an even more widespread use. Targeted NGS has been proven useful for the molecular diagnosis of many, but not all, cases with a provisional diagnosis of non-HFE HH after first level genetic testing (i.e. searching for the classical C282Y/H63D variants on the HFE gene). Among the interesting findings, digenic inheritance, i.e. compound heterozygosity for mutations in different genes proven to be causal, appears to occur not infrequently. Similarly, the substantial fraction of cases that remain unexplained after deep sequencing of the known five HH genes suggests that novel HH gene(s) have yet to be discovered. WES represents an attractive option for undiagnosed case. However, the long route from rough data produced by the sequencer to a plausible clinical diagnosis is challenging, and requires a close and constant collaboration between bioinformaticians and expert clinicians. Moreover, collaboration among Referral Centers, as well as the development of disease registries are both instrumental for proper advance in knowledge. 4 Oral abstracts Feb 8 – Session 2 How to define the need of iron supplementation in anaemia of inflammation and chronic kidney disease Prof. Igor Theurl University Hospital, Innsbruck Anaemia of chronic disease resulting from, for example, chronic kidney disease, cancer or autoimmune disease is the second most prevalent form of anaemia after iron deficiency anaemia and becomes even the most prevalent form within an in-patient setting. Despite its high prevalence and its significant impact on patient health and wellbeing, anaemia of chronic disease is often misdiagnosed and therefore poorly treated. This form of anaemia is driven by multiple factors including EPO deficiency and resistance, a direct negative effect on red blood cell precursors, reduced red blood cell survival and the reduced availability of iron due to misdistribution within the body. Anaemia of chronic disease is not driven by iron deficiency, but by a reduced availability of functional iron in the blood. Routine laboratory tests are usually only designed to detect iron deficiency, making the diagnosis of anaemia of chronic disease challenging. However, in most cases, the correct diagnosis of this form can be achieved quickly and at relatively low cost. This requires a better understanding of options and limitations of the iron and erythropoiesis tests available to the physician, coupled with a deeper understanding of the known pathology of the underlying disease. Each form of anaemia has a different set of treatment options and since there is a growing number of novel and expensive treatments, it is critical to determine the correct diagnosis to prescribe the best treatment. To benefit patients and to reduce overall healthcare costs, it is essential to establish standardised laboratory indicators and decision trees to guide diagnosis and optimal treatment. 5 Oral abstracts Feb 8 – Session 2 Intravenous iron for non-anemic patients – the heart failure clinical story 2000-2018. Professor Stefan D Anker, MD PhD Division of Cardiology and Metabolism; Department of Cardiology (CVK); Berlin-Brandenburg Center for Regenerative Therapies (BCRT); Charité Universitätsmedizin Berlin, Germany. [email protected] Iron is importantly involved in numerous physiological processes including oxygen transport
Load more

Recommended publications
  • Diagnosis and Treatment of Genetic HFE-Hemochromatosis: the Danish Aspect
    Review Gastroenterol Res. 2019;12(5):221-232 Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect Nils Thorm Milmana, d, Frank Vinholt Schioedta, Anders Ellekaer Junkerb, Karin Magnussenc Abstract hemochromatosis. Among people of Northwestern European descent including ethnic Danes, HFE-hemochromatosis is by This paper outlines the Danish aspects of HFE-hemochromatosis, far the most common, while non-HFE hemochromatosis oc- which is the most frequent genetic predisposition to iron overload curs sporadically [1]. in the five million ethnic Danes; more than 20,000 people are ho- The Danish National Board of Health in 2017 assigned mozygous for the C282Y mutation and more than 500,000 people are the handling (evaluation, diagnosis and treatment) of patients compound heterozygous or heterozygous for the HFE-mutations. The with hemochromatosis to the specialty of gastroenterology and disorder has a long preclinical stage with gradually increasing body hepatology thereby terminating many years of frustration in iron overload and eventually 30% of men will develop clinically overt these “homeless” patients, who, due to their plethora of symp- disease, presenting with symptoms of fatigue, arthralgias, reduced li- toms, are referred from one specialty to another in order to bido, erectile dysfunction, cardiac disease and diabetes. Subsequently obtain a diagnosis. This review is based on the Danish Na- the disease may progress into irreversible arthritis, liver cirrhosis, tional Guidelines for HFE-hemochromatosis elaborated by the cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective Danish Society for Gastroenterology and Hepatology [2]. The standard treatment is repeated phlebotomies, which in the preclinical figures and text boxes are reproduced with permission from the and early clinical stages ensures a normal survival rate.
    [Show full text]
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • Effect of Genotype on Micronutrient Absorption and Metabolism: a Review of Iron, Copper, Iodine and Selenium, and Folates Richard Mithen
    Int. J. Vitam. Nutr. Res., 77 (3), 2007, 205–216 Effect of Genotype on Micronutrient Absorption and Metabolism: a Review of Iron, Copper, Iodine and Selenium, and Folates Richard Mithen Institute of Food Research, Colney Lane, Norwich, NR4 7UA, UK Received for publication: July 28, 2006 Abstract: For the majority of micronutrients, there are very little data, or none at all, on the role of genetic poly- morphisms on their absorption and metabolism. In many cases, the elucidation of biochemical pathways and regulators of homeostatic mechanisms have come from studies of individuals that have mutations in certain genes. Other polymorphisms in these genes that result in a less severe phenotype may be important in determining the natural range of variation in absorption and metabolism that is commonly observed. To illustrate some of these aspects, I briefly review the increased understanding of iron metabolism that has arisen from our knowledge of the effects of mutations in several genes, the role of genetic variation in mediating the nutritional effects of io- dine and selenium, and finally, the interaction between a genetic polymorphism in folate metabolism and folic acid fortification. Key words: Micronutrients, genetic polymorphisms, iron, iodine, selenium, folates Introduction the interpretation of epidemiological studies, in which some of the variation observed in nutrient status or re- Recently there has been considerable interest in the role quirement may be due to genetic variation at a few or sev- that genetic polymorphisms may play in several aspects eral loci that determine the uptake and metabolism of var- of human nutrition, and the ill-defined terms nutrige- ious nutrients.
    [Show full text]
  • The Potential for Transition Metal-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis
    REVIEW ARTICLE published: 23 July 2014 AGING NEUROSCIENCE doi: 10.3389/fnagi.2014.00173 The potential for transition metal-mediated neurodegeneration in amyotrophic lateral sclerosis David B. Lovejoy* and Gilles J. Guillemin Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia Edited by: Modulations of the potentially toxic transition metals iron (Fe) and copper (Cu) are impli- Roger S. Chung, Macquarie cated in the neurodegenerative process in a variety of human disease states including University, USA amyotrophic lateral sclerosis (ALS). However, the precise role played by these metals is Reviewed by: Junming Wang, University of still very much unclear, despite considerable clinical and experimental data suggestive of Mississippi Medical Center, USA a role for these elements in the neurodegenerative process.The discovery of mutations in Ramon Santos El-Bachá, Universidade the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD-1) in ALS patients established Federal da Bahia, Brazil the first known cause of ALS. Recent data suggest that various mutations in SOD-1 affect *Correspondence: metal-binding of Cu and Zn, in turn promoting toxic protein aggregation. Copper home- David B. Lovejoy, Macquarie University, Australian School of ostasis is also disturbed in ALS, and may be relevant to ALS pathogenesis. Another set Advanced Medicine, Motor Neuron of interesting observations in ALS patients involves the key nutrient Fe. In ALS patients, and Neurodegenerative Diseases Fe loading can be inferred by studies showing increased expression of serum ferritin, an Research Group, Building F10A, 2 Fe-storage protein, with high serum ferritin levels correlating to poor prognosis. Magnetic Technology Place, NSW, 2109, Australia resonance imaging of ALS patients shows a characteristic T2 shortening that is attributed e-mail: [email protected] to the presence of Fe in the motor cortex.
    [Show full text]
  • HHC Disorder Setting
    DISORDER/SETTING Question 1: What is the specific clinical disorder to be studied? Question 2: What are the clinical findings defining this disorder? Question 3: What is the clinical setting in which the test is to be performed? Question 4: What DNA test(s) are associated with this disorder? Question 5: Are preliminary screening questions employed? Question 6: Is it a stand-alone test or is it one of a series of tests? Question 7: If it is part of a series of screening tests, are all tests performed in all instances (parallel) or are only some tests performed on the basis of other results (series)? ACCE Review of HHC/Adult General Population Disorder/Setting 1-1 Version 2003.6 DISORDER/SETTING Question 1: What is the specific clinical disorder to be studied? The specific clinical disorder is primary iron overload of adult onset sufficient to cause significant morbidity and mortality. • Iron overload refers to excess deposition of iron in parenchymal cells in the liver, pancreas and heart, and/or increased total body mobilizable iron. • Primary refers to a genetically determined abnormality of iron absorption, metabolism, or both. • Morbidity refers to organ damage that results in physical disability over and above that seen in the absence of iron overload. A single inherited disorder, HFE-related hereditary hemochromatosis (HHC) accounts for the vast majority of cases of primary iron overload in Caucasian adults in the United States. The HFE gene is linked to HLA-A on the short arm of chromosome 6. HFE-related HHC is a recessive disorder. A small proportion of primary iron overload cases is explained by inherited disorders other than HFE-related HHC.
    [Show full text]
  • Revisiting Hemochromatosis: Genetic Vs
    731 Review Article on Unresolved Basis Issues in Hepatology Page 1 of 16 Revisiting hemochromatosis: genetic vs. phenotypic manifestations Gregory J. Anderson1^, Edouard Bardou-Jacquet2 1Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute and School of Chemistry and Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; 2Liver Disease Department, University of Rennes and French Reference Center for Hemochromatosis and Iron Metabolism Disease, Rennes, France Contributions: (I) Conception and design: Both authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors. Correspondence to: Gregory J. Anderson. Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, Queensland 4006, Australia. Email: [email protected]. Abstract: Iron overload disorders represent an important class of human diseases. Of the primary iron overload conditions, by far the most common and best studied is HFE-related hemochromatosis, which results from homozygosity for a mutation leading to the C282Y substitution in the HFE protein. This disease is characterized by reduced expression of the iron-regulatory hormone hepcidin, leading to increased dietary iron absorption and iron deposition in multiple tissues including the liver, pancreas, joints, heart and pituitary. The phenotype of HFE-related hemochromatosis is quite variable, with some individuals showing little or no evidence of increased body iron, yet others showing severe iron loading, tissue damage and clinical sequelae. The majority of genetically predisposed individuals show at least some evidence of iron loading (increased transferrin saturation and serum ferritin), but a minority show clinical symptoms and severe consequences are rare.
    [Show full text]
  • Effect-Of-Various-Calcium-Salts.Pdf
    Journal of Trace Elements in Medicine and Biology 49 (2018) 8–12 Contents lists available at ScienceDirect Journal of Trace Elements in Medicine and Biology journal homepage: www.elsevier.com/locate/jtemb Effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age T Valeria Candiaa, Israel Ríos-Castilloa,b, Frank Carrera-Gilc, Berta Vizcarraa, Manuel Olivaresa, ⁎ Sotiris Chaniotakisd, Fernando Pizarroa, a Laboratory of Micronutrients, Institute of Nutrition and Food Technologies, University of Chile, Santiago, Chile b Food and Agriculture Organization of the United Nations, Sub Regional Office for Mesoamerica. Panama City, Panama c Nutrition and Dietetic Department, Fundación Valle del Lili Academic Hospital, Cali, Colombia d Department of Graduate Medical Sciences, Boston University School of Medicine, Boston, United States ARTICLE INFO ABSTRACT Keywords: Introduction: Micronutrient deficiencies are one of the most important public health issues worldwide and iron Iron bioavailability (Fe) deficiency anemia is the most prevalent micronutrient deficiency. Iron deficiency often coexists with cal- Iron absorption cium deficiency and iron and calcium supplementation often overlap. This has led to investigations into the Iron interaction between these two minerals, and whether calcium may inhibit iron absorption in the gut. Calcium Objective: To determine the effect of various calcium salts on non-heme iron bioavailability in fasted women of Women childbearing age. Methods: A randomized and single blinded trial was conducted on 27 women of childbearing age (35–45 years old) divided into 2 groups (n1 = 13 and n2 = 14, respectively). On four different days, after an overnight fast, 55 59 they received 5 mg of Fe as FeSO4 (labeled with Fe or Fe) with 800 mg of elemental calcium in the form of either calcium chloride, calcium gluconate, calcium citrate, calcium carbonate, calcium lactate, calcium sulfate or calcium phosphate.
    [Show full text]
  • Copper, Magnesium, Zinc and Calcium Status in Osteopenic and Osteoporotic Post-Menopausal Women
    02-Mahdaviroshan_- 25/05/15 15:48 Pagina 18 Mini-review Copper, magnesium, zinc and calcium status in osteopenic and osteoporotic post-menopausal women Marjan Mahdavi-Roshan 1 seems to be due to an imbalance between bone resorption and Mehrangiz Ebrahimi 2 bone formation at older ages (1-3), and is widely recognized as Aliasgar Ebrahimi 3 a major public health problem, especially for women (4). Osteopenia, defined as a bone mineral density that is lower than normal but not low enough to be classified as osteo - 1 Department of Community Medicine, School of Medicine, porosis, generally increases in severity with age and is most Guilan University of Medical Science, Rasht, Iran prevalent in women who are postmenopausal. Osteopenia is 2 Faculty of Health and Nutrition Sciences, Tabriz University often called ‘pre-osteoporosis’ as it sometimes leads to os - of Medical Sciences, Tabriz, Iran teoporosis (5). The etiology of osteoporosis and osteopenia 3 Department of Rheumatology, School of Medicine, Tabriz, is multi-factorial. Many factors – genetic differences, en - University of Medical Sciences, Tabriz, Iran docrine factors and lifestyle behaviour, such as physical ac - tivity and diet, especially mineral deficiency due to reduced dietary intake and reduced absorption of these nutrients – are thought to play important role in osteopenia or osteo - Address for correspondence: porosis and its prevention (5, 6). Marjan Mahdavi-Roshan Minerals such as magnesium, zinc, copper and calcium are Department of Community Medicine all essential for health. They help promote strong bones and School of Medicine, Guilan University of Medical Science are involved in the interaction of more than 300 enzyme re - Rasht, Iran actions.
    [Show full text]
  • Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications
    International Journal of Molecular Sciences Review Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications Gra˙zynaGromadzka 1,*, Beata Tarnacka 2 , Anna Flaga 1 and Agata Adamczyk 3 1 Collegium Medicum, Faculty of Medicine, Cardinal Stefan Wyszynski University, Wóycickiego 1/3 Street, 01-938 Warsaw, Poland; a.fl[email protected] 2 Department of Rehabilitation, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Rehabilitation Clinic, Medical University of Warsaw, Sparta´nska1 Street, 02-637 Warsaw, Poland; [email protected] 3 Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawi´nskiegoStreet, 02-106 Warsaw, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-5-1071-7110 Received: 6 November 2020; Accepted: 28 November 2020; Published: 4 December 2020 Abstract: Copper is one of the most abundant basic transition metals in the human body. It takes part in oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining the integrity of blood vessels, as well as in iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cell signaling and may participate in modulation of membrane receptor-ligand interactions, control of kinase and related phosphatase functions, as well as many cellular pathways. Its role is also important in controlling gene expression in the nucleus. In the nervous system in particular, copper is involved in myelination, and by modulating synaptic activity as well as excitotoxic cell death and signaling cascades induced by neurotrophic factors, copper is important for various neuronal functions. Current data suggest that both excess copper levels and copper deficiency can be harmful, and careful homeostatic control is important.
    [Show full text]
  • Pathophysiological Consequences and Benefits of HFE Mutations: 20 Years of Research
    Pathophysiological consequences and benefits of HFE mutations: 20 years of research | Haematologica 19.05.17 12:55 EHA search & Advanced Search Home Current Issue Ahead Of Print Archive Submit a Manuscript About Us More Pathophysiological Consequences And Benefits Of HFE Mutations: 20 Years Of Research Ina Hollerer, André Bachmann, Martina U. Muckenthaler Haematologica May 2017 102: 809-817; Doi:10.3324/haematol.2016.160432 AUTHOR AFFILIATIONS Article Figures & Data Info & Metrics ! PDF Vol 102 Issue 5 Abstract Table of Contents Table of Contents Mutations in the HFE (hemochromatosis) gene cause hereditary (PDF) hemochromatosis, an iron overload disorder that is hallmarked by About the Cover excessive accumulation of iron in parenchymal organs. The HFE Index by author 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 " Email © Request research findings about hereditary hemochromatosis, and outline # Print Permissions the pathological consequences of the associated gene defects. In $ Citation Tools % Share addition, we discuss potential advantages of HFE mutations in asymptomatic carriers. Tweet Gefällt mir 55 Introduction Alert me when this article is cited http://www.haematologica.org/content/102/5/809 Seite 1 von 22 Pathophysiological consequences and benefits of HFE mutations: 20 years of research | Haematologica 19.05.17 12:55 Iron plays a key role in various physiological pathways. All cells of Alert me if a correction is posted the human body contain iron as an integral part of FeS-proteins.
    [Show full text]
  • Diagnosis and Treatment of Genetic HFE-Hemochromatosis: the Danish Aspect
    Diagnosis and Treatment of Genetic HFE-Hemochromatosis The Danish Aspect Milman, Nils Thorm; Schioedt, Frank Vinholt; Junker, Anders Ellekaer; Magnussen, Karin Published in: Gastroenterology Research DOI: 10.14740/gr1206 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): Milman, N. T., Schioedt, F. V., Junker, A. E., & Magnussen, K. (2019). Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect. Gastroenterology Research, 12(5), 221-232. https://doi.org/10.14740/gr1206 Download date: 02. okt.. 2021 Review Gastroenterol Res. 2019;12(5):221-232 Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect Nils Thorm Milmana, d, Frank Vinholt Schioedta, Anders Ellekaer Junkerb, Karin Magnussenc Abstract hemochromatosis. Among people of Northwestern European descent including ethnic Danes, HFE-hemochromatosis is by This paper outlines the Danish aspects of HFE-hemochromatosis, far the most common, while non-HFE hemochromatosis oc- which is the most frequent genetic predisposition to iron overload curs sporadically [1]. in the five million ethnic Danes; more than 20,000 people are ho- The Danish National Board of Health in 2017 assigned mozygous for the C282Y mutation and more than 500,000 people are the handling (evaluation, diagnosis and treatment) of patients compound heterozygous or heterozygous for the HFE-mutations. The with hemochromatosis to the specialty of gastroenterology and disorder has a long preclinical stage with gradually increasing body hepatology thereby terminating many years of frustration in iron overload and eventually 30% of men will develop clinically overt these “homeless” patients, who, due to their plethora of symp- disease, presenting with symptoms of fatigue, arthralgias, reduced li- toms, are referred from one specialty to another in order to bido, erectile dysfunction, cardiac disease and diabetes.
    [Show full text]
  • Reviews on the Mineral Provision in Ruminants (VIII): IRON METABOLISM and REQUIREMENTS in RUMINANTS
    Reviews on the mineral provision in ruminants (VIII): IRON METABOLISM AND REQUIREMENTS IN RUMINANTS A.M. van den Top CVB Documentation report nr. 40 November 2005 Centraal Veevoederbureau Centraal Veevoederbureau 2005 All rights are explicitly reserved. No part of this publication may be reproduced, distributed and/or published by any means (including but not limited to printing, photocopying, microfilming, scanning, electronic copying or distribution) in whatever manner, without the prior written consent of the Centraal Veevoederbureau. Although this publication has been compiled with great care, the Centraal Veevoederbureau cannot be held liable in any way for the consequences of any use of the information contained in this publication. Reviews on the mineral provision in ruminants (VIII): IRON METABOLISM AND REQUIREMENTS IN RUMINANTS A.M. van den Top Adviesbureau VOER-RAAD Groenekan, The Netherlands CVB Documentation report nr. 40 November 2005 Centraal Veevoederbureau Postbus 2176 8203 AD Lelystad Telefoon 0320 – 29 32 11 Telefax 0320 – 29 35 38 E-mail [email protected] Internet www.cvb.pdv.nl PREFACE In the Netherlands the ´Handleiding Mineralenonderzoek bij rundvee in de praktijk´1 is a well- known publication that has been used already for decades as a guide to trace and treat mineral disorders in cattle. The fifth edition of this guidebook was published in 1996. The content of this publication was largely identical to that of the fourth edition (1990). Therefore the (independent) committee that is responsible for the contents of the guidebook (the ‘Commissie Onderzoek Minerale Voeding’2, COMV) decided in 2000 that a thorough revision was desired. The committee was of the opinion that, if possible, the available scientific literature should be summarized and evaluated once again.
    [Show full text]