DOCSLIB.ORG

Iron Overload

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Iron Overload Matt McCollough, M.D. GI Grand Rounds March 20, 2008 Case y 77 year‐old white female y Referred to Hepatology Clinic for asymptomatic elevation of transferrin saturation level Case y Past Medical Hx: y HLD y HTN y OA y Schatzki’s ring s/p dilt for dysphagia y Bilateral Breast CA s/p bil mastectomy y s/p complete hysterectomy y cataracts Case y Medications: y Lipitor 10mg daily y Avalide 150/125mg daily y Calcium + D daily y Glucosamine/Chondroitin daily y Ibuprofen 400‐800mg daily y Allergies ‐ PCN Case y Social Hx: y Retired secretary y Widowed y Three 12 oz cans of beer daily y Denies tobacco, IVDU, tattoos y Family Hx: y M ‐ Cerebral hemorrhage, deceased 67 y F‐ CVA, deceased 72 y B ‐Oat cell lung Ca, deceased 52 Case y ROS: y Positives: moderate knee pain bilaterally y Denies: jaundice, diabetes, darkening of skin, dyspnea, orthopnea, swelling, abdominal pain Case y Physical Exam: y BP 173/86, P 77, R, 19, T 97.5, Ht 5’6”, Wgt 178 y ++Crepitis in knees bilaterally y Normal heart and lungs y No icterus, jaundice, spiders, hepatomegaly, splenomegaly or skin discoloration Case y Laboratories: y WBC 5.9 y BUN 12 y Hgb 13.8 y Cr 0.7 y MCV 97 y Glu 98 y Plt 203 y TG 77 y AlkP 120 y AST 27 y IBC 226 y ALT 33 y Fe 187 y TB 0.7 y % sat 83 y DB 0.17 y Ferritin 380 y TP 6.9 y Alb 4.4 Case y A diagnostic test was performed… Objectives y Review the pathophysiology of iron overload and hemochromatosis y Identify non‐HFE iron overload mutations and causes of secondary iron overload y Review AASLD Guidelines for Diagnosis and Management of Hereditary Hemochromatosis (HH) What is normal anyway? y Normal total body iron content is 3‐4 grams y Hemoglobin 2.5 g y Ferritin and hemosiderin 1 g (men) y Proteins (myoglobin, cytochromes, catalase) 400 mg y Transferrin bound 3‐7 mg Pluses and Minuses y Absorption y Dietary absorption is regulated so that it matches daily iron loss (Increased absorption in deficient states) y Mostly through the duodenum y Western diet 10‐20mg/day y About 10% absorbed y Losses y Sweat, shed skin cells, ?gi (1mg/day) y Premenopausal adult women (0.5 – 1.0mg/day) Pathophysiology of Hemochromatosis y Mechanisms y Alterations in HFE protein function y Increased intestinal absorption of dietary iron y Iron induced tissue injury and fibrosis HFE protein y Structure is similar to major histocompatibility complex (MHC) class I molecules but does not present antigen y The HFE protein forms a complex with the transferrin receptor (TfR1) which effects cellular Fe uptake y It may also participate with transferrin receptor (TfF2) to regulate hepcidin which acts to reduce dietary iron absorption and inhibit iron release by macrophages Hepcidin y Produced in the liver y Possible iron storage regulator y Inhibits iron absorption in the small intestine and prevents release of iron from macrophages y Levels are low in HH y Is an acute phase reactant and plays a central role in anemia of chronic disease (levels are high) Duodenal absorption Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed Duodenal iron absorption y Regulated by: y Demands of erythropoesis independent of iron stores y Storage regulator (i.e. hepcidin) that prevents iron overload when needs are met Iron Toxicity y Increased iron causes saturation of circulating transferrin which leads to more “non‐transferrin‐ bond” iron y Iron tends to deposit in cells with high levels of transferrin receptors (i.e. heart, liver, thyroid, gonads, pancreatic islets) y Reactive oxygen species attack lipids, proteins, RNA and DNA causing tissue damage and fibrosis HH Stages of iron Years Parenchymal iron overload storage (grams) Insignificant 0-20 0-5 Iron overload 20-40 10-20 without disease Iron overload with >40 >20 organ damage Causes of Iron Overload y There is NO mechanism for increasing iron excretion, therefore, overload will ensue if there is excess absorption y Genetic (Increased iron absorption with normal intake) y Chronic liver diseases y Iatrogenic (Surely, it wasn’t my fault?) Secondary Iron overload (Acquired) Iron‐loading anemias Parenteral Iron overload y Thalassemia major y RBC transfusion y Sideroblastic anemia y IV iron y Chronic hemolytic anemia y Long‐term hemodialysis y Aplastic anemia y Pyruvate kinase deficiency y Pyridoxine‐responsive anemia Secondary Iron overload (Acquired) Chronic liver disease Other y HCV y Dietary iron overload y HBV y Dysmetabolic iron overload y Alcoholic liver disease syndrome y NASH y Porphyria cutanea tarda y Portacaval shunt Clinical Presentation y Symptomatic iron overload usually occurs after the 5th decade y Expression is influenced by age, sex, dietary iron, blood loss and unknown factors y Women express the disease less frequently than men y Alcohol and Hepatitis C may accelerate the disease expression Symptoms Occurrence, % Weakness, lethargy, fatigue 40–85 Apathy, lack of interest 40–85 Abdominal pain 30–60 Weight loss 30–60 Arthralgias 40–60 Loss of libido, impotence 30–60 Amenorrhea 20–60 Congestive heart failure 0–40 symptoms Bacon BR, Powell LW, Adams PC, et al. Molecular medicine and hemochromatosis: at the crossroads. Gastroenterology. 1999. 116:193-207. Edwards CQ, Cartwright GE, Skolnick MH, et al. Homozygosity for hemochromatosis: Clinical manifestations. Ann Intern Med. 1980. 93:511-525. Hereditary Hemochromatosis (HH) y “Several inherited disorders of iron homeostasis characterized by increased intestinal iron absorption resulting in tissue iron deposition” Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. HH y HFE‐related y C282Y homozygosity y C282Y/H63D compound heterozygosity y Other HFE mutations y Non‐HFE‐related y Hemojuvelin (HJV) mutations y Hepcidin (HAMP) mutations y Transferrin receptor 2 (TfR2) mutations y Ferroportin 1 (SLC40A1) mutations HH (alternate nomenclature) y Type 1 (HFE) y Type 2 (Hemojuvelin/Hepcidin) y Type 3 (Transferrin Receptor 2) y Type 4 (Ferroportin) HFE‐related HH y The most common genetic disorder in the Caucasian population, especially northern European (Nordic, Celtic) y Autosomal recessive y Prevalence for homozygotic mutation in U.S. whites is 1:200‐250 y 1:10 are heterozygous carriers HFE Gene y The clinically significant gene mutations are C282Y and H63D y C282Y y Described in 1996 y G to A missense mutation y Substitutes tyrosine for cysteine y 60‐93% of patients with iron overload are C282Y homozygous HFE Gene y Prevalence of compound heterozygotes (C282Y/H63D) is 1‐2 % y Only a small percentage of compound heterozygotes will develop iron overload y A negative HFE gene test does not exclude iron overload HFE‐Gene y All C282Y homozygotes had elevated transferrin saturation (100% positive predictive accuracy) y C282Y homozygotes –full expression with progressive tissue iron overload in 58% y The rate of iron accumulation is variable Olynyk JK, et al. A population based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999;341:718-724. Hemojuvelin and Hepcidin y Hemojuvelin (HJV/1q) Mutation y Hepcidin Antimicrobial Peptide (HAMP/19q13.1) Mutation y “Juvenile Hemochromatosis” y Autosomal recessive y HJV is a regulator of hepcidin y Very low hepcidin causes massive Fe influx. y High ferritin and transferrin saturation in 1st decade. y Hypogonadism before end of 2nd decade, cardiac disease & abdominal pain y Cirrhosis occurs later y Death during 3rd decade from heart failure Transferrin Receptor 2 (TfR2) y Located on hepatocytes y Autosomal recessive mutation y TfR2 is regulator of hepcidin ‐> Low hepcidin ‐>causes increased Fe influx. y High transferrin saturation in 2nd to 3rd decades y HHC may develop from 2nd to 4th decades y Mild to severe Fe overload in periportal hepatocytes y Hypochromic anemia Ferroportin y Missense mutation of ferroportin 1 gene y Iron exporter located in enterocytes, macrophages, and hepatocytes y Rare autosomal dominant mutations Ferroportin y Worldwide distribution y Decreased Fe efflux y High ferritin in 1st decade y Fe deposit in RES with very high ferritin but low or normal transferrin saturation; high saturation late in life. y Mild hypochromic anemia. y Mild liver injury with sinusoidal fibrosis y May cause cirrhosis y Treatment: Phlebotomy q 2‐3 weeks (not weekly) African Iron Overload y Sub‐Saharan Africa y Non‐HFE related genetic trait (? Ferroportin 1) exacerbated by dietary iron loading (maize beverage) y Iron loaded Kupffer cells y This contrasts HFE‐related HH were Kupffer cells are spared Aceruloplasminemia y Autosomal recessive y Decreased Fe efflux y Lack of ceruloplasmin, which has ferroxidase activity needed to release Fe from cells y Causes deposit in the: y basal ganglia, dentate nucleus (ataxia and dementia) y Pancreas (diabetes mellitus) y RES (hypochromic microcytic anemia) y Liver disease is mild y Treatment: Chelation, Exjade® (deferasirox) & desferoxamine Other y Atransferrinemia/Hypotransferrinemia y Autosomal recessive y Increased Fe influx y Severe anemia y Onset in 1st & 2nd decade y H‐Ferritin associated hereditary Fe‐Overload y Autosomal dominant y Increased Fe influx y Liver Fe overload in 4th‐5th decade Diagnosis and Management of Hereditary Hemochromatosis 2001 Management Objectives for HH y Early diagnosis to prevent organ damage and dysfunction due to tissue iron toxicity y Screening and early detection of asymptomatic HH cases to reduce mortality y Recognition and diagnosis of symptomatic cases of HH, to minimize progression and complications of the disease y Adequate treatment of HH to promote rapid, safe, and effective removal of iron y Vigilant follow‐up and maintenance treatment of all cases of HH Tavill, A. Diagnosis and Management of Hemochromatosis. Hep May 2001. Who gets screened? y Symptomatic patients y Unexplained liver disease or known liver disease with abnormal serum iron studies y Type 2 DM especially with hepatomegaly, abnormal lft’s, atypical cardiac disease, and/or early onset sexual dysfunction y Early‐onset atypical arthropathy, cardiac disease, male sexual dysfunction Tavill, A.
Load more

Recommended publications
  • Iron Dysregulation in Movement Disorders
    Neurobiology of Disease 46 (2012) 1–18 Contents lists available at SciVerse ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi Review Iron dysregulation in movement disorders Petr Dusek a,c, Joseph Jankovic a,⁎, Weidong Le b a Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA b Parkinson's Disease Research Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA c Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic article info abstract Article history: Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination Received 9 November 2011 and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic Revised 22 December 2011 disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly Accepted 31 December 2011 involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid Available online 12 January 2012 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked Keywords: Iron to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzymes or transporters Neurodegeneration such as ATP13A2, mucolipin-1 and possibly also β-galactosidase and α-fucosidase. Increased cellular iron uptake Dystonia in these diseases may be caused by impaired recycling of iron which normally involves lysosomes.
    [Show full text]
  • Nutrient Deficiency and Drug Induced Cardiac Injury and Dysfunction
    Editorial Preface to Hearts Special Issue “Nutrient Deficiency and Drug Induced Cardiac Injury and Dysfunction” I. Tong Mak * and Jay H. Kramer * Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington DC, WA 20037, USA * Correspondence: [email protected] (I.T.M.); [email protected] (J.H.K.) Received: 30 October 2020; Accepted: 1 November 2020; Published: 3 November 2020 Keywords: cardiac injury/contractile dysfunction; micronutrient deficiency; macromineral deficiency or imbalance; impact by cardiovascular and/or anti-cancer drugs; systemic inflammation; oxidative/nitrosative stress; antioxidant defenses; supplement and/or pathway interventions Cardiac injury manifested as either systolic or diastolic dysfunction is considered an important preceding stage that leads to or is associated with eventual heart failure (HF). Due to shifts in global age distribution, as well as general population growth, HF is the most rapidly growing public health issue, with an estimated prevalence of approximately 38 million individuals globally, and it is associated with considerably high mortality, morbidity, and hospitalization rates [1]. According to the US Center for Disease Control and The American Heart Association, there were approximately 6.2 million adults suffering from heart failure in the United States from 2013 to 2016, and heart failure was listed on nearly 380,000 death certificates in 2018 [2]. Left ventricular systolic heart failure means that the heart is not contracting well during heartbeats, whereas left ventricular diastolic failure indicates the heart is not able to relax normally between beats. Both types of left-sided heart failure may lead to right-sided failure. There have been an increasing number of studies recognizing that the deficiency and/or imbalance of certain essential micronutrients, vitamins, and macrominerals may be involved in the pathogenesis of cardiomyopathy/cardiac injury/contractile dysfunction.
    [Show full text]
  • Secondary Hemochromatosis As a Result of Acute Transfusion-Induced Iron Overload in a Burn Patient Michael Amatto1 and Hernish Acharya2*
    Amatto and Acharya Burns & Trauma (2016) 4:10 DOI 10.1186/s41038-016-0034-z CASE REPORT Open Access Secondary hemochromatosis as a result of acute transfusion-induced iron overload in a burn patient Michael Amatto1 and Hernish Acharya2* Abstract Background: Red blood cell transfusions are critical in burn management. The subsequent iron overload that can occur from this treatment can lead to secondary hemochromatosis with multi-organ damage. Case Presentation: While well recognized in patients receiving chronic transfusions, we present a case outlining the acute development of hemochromatosis secondary to multiple transfusions in a burn patient. Conclusions: Simple screening laboratory measures and treatment options exist which may significantly reduce morbidity; thus, we believe awareness of secondary hemochromatosis in those treating burn patients is critical. Keywords: Secondary hemochromatosis, Transfusion, Iron overload, Burn patients Background of parental iron or RBC transfusions, neonatal iron over- Acute and chronic treatment of the severely burned indi- load, aceruloplasminemia, and African iron overload [6, 7]. vidual is often complex due to many physical and psycho- Hemochromatosis is a disease characterized by iron logical factors [1, 2]. Resuscitation involving packed red accumulation in tissues. Initial symptoms and signs in- blood cell (RBC) transfusion is often essential [3]. How- clude skin pigmentation, fatigue, erectile dysfunction, ever, RBC transfusion carries potential risks including and arthralgia while later stages of the disease result in hemolytic reactions and infections, as well as other com- cardiomyopathy, diabetes mellitus, hypogonadism, hypo- plications that are often overlooked such as iron overload pituitarism, and hypoparathyroidism, as well as liver fi- [4, 5]. Each unit of RBCs contains 200–250 mg of iron, brosis and cirrhosis which can lead to hepatocellular and with no physiologic excretion mechanism, multiple carcinoma [6].
    [Show full text]
  • Orphanet Report Series Rare Diseases Collection
    Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic
    [Show full text]
  • Mackenzie's Mission Gene & Condition List
    Mackenzie’s Mission Gene & Condition List What conditions are being screened for in Mackenzie’s Mission? Genetic carrier screening offered through this research study has been carefully developed. It is focused on providing people with information about their chance of having children with a severe genetic condition occurring in childhood. The screening is designed to provide genetic information that is relevant and useful, and to minimise uncertain and unclear information. How the conditions and genes are selected The Mackenzie’s Mission reproductive genetic carrier screen currently includes approximately 1300 genes which are associated with about 750 conditions. The reason there are fewer conditions than genes is that some genetic conditions can be caused by changes in more than one gene. The gene list is reviewed regularly. To select the conditions and genes to be screened, a committee comprised of experts in genetics and screening was established including: clinical geneticists, genetic scientists, a genetic pathologist, genetic counsellors, an ethicist and a parent of a child with a genetic condition. The following criteria were developed and are used to select the genes to be included: • Screening the gene is technically possible using currently available technology • The gene is known to cause a genetic condition • The condition affects people in childhood • The condition has a serious impact on a person’s quality of life and/or is life-limiting o For many of the conditions there is no treatment or the treatment is very burdensome for the child and their family. For some conditions very early diagnosis and treatment can make a difference for the child.
    [Show full text]
  • A Curated Gene List for Reporting Results of Newborn Genomic Sequencing
    © American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE A curated gene list for reporting results of newborn genomic sequencing Ozge Ceyhan-Birsoy, PhD1,2,3, Kalotina Machini, PhD1,2,3, Matthew S. Lebo, PhD1,2,3, Tim W. Yu, MD3,4,5, Pankaj B. Agrawal, MD, MMSC3,4,6, Richard B. Parad, MD, MPH3,7, Ingrid A. Holm, MD, MPH3,4, Amy McGuire, PhD8, Robert C. Green, MD, MPH3,9,10, Alan H. Beggs, PhD3,4, Heidi L. Rehm, PhD1,2,3,10; for the BabySeq Project Purpose: Genomic sequencing (GS) for newborns may enable detec- of newborn GS (nGS), and used our curated list for the first 15 new- tion of conditions for which early knowledge can improve health out- borns sequenced in this project. comes. One of the major challenges hindering its broader application Results: Here, we present our curated list for 1,514 gene–disease is the time it takes to assess the clinical relevance of detected variants associations. Overall, 954 genes met our criteria for return in nGS. and the genes they impact so that disease risk is reported appropri- This reference list eliminated manual assessment for 41% of rare vari- ately. ants identified in 15 newborns. Methods: To facilitate rapid interpretation of GS results in new- Conclusion: Our list provides a resource that can assist in guiding borns, we curated a catalog of genes with putative pediatric relevance the interpretive scope of clinical GS for newborns and potentially for their validity based on the ClinGen clinical validity classification other populations. framework criteria, age of onset, penetrance, and mode of inheri- tance through systematic evaluation of published evidence.
    [Show full text]
  • Central Nervous System Involvement in a Rare Genetic Iron Overload Disorder
    Case report Central nervous system involvement in a rare genetic iron overload disorder C. Bethlehem*, B. van Harten, M. Hoogendoorn Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands, *corresponding author: tel.: +31 (0)58-286 38 12, e-mail: [email protected] a b s t r a C t in most genetic iron overload disorders the diagnosis can what was known on this topic? be rejected when transferrin saturation is low. we describe The diagnostic approach in patients suspected a patient and her family with hyperferritinaemia and for hereditary haemochromatosis is focused low transferrin saturation with iron accumulation in the on hyperferritinaemia and a high transferrin central nervous system (CNS) and liver due to hereditary saturation due to the high frequency of HFE-related aceruloplasminaemia. in this rare genetic iron overload haemochromatosis. disorder oxidation of iron is disturbed, resulting in storage of iron in the CNS and visceral organs. what does this add? Hyperferritinaemia in combination with a low transferrin saturation does not always exclude K e y w o r d s an iron overload disorder. Particularly when neurological symptoms occur in the presence Iron overload disorder, hereditary aceruloplasminaemia, of persistent hyperferritinaemia, hereditary hereditary haemochromatosis aceruloplasminaemia needs to be excluded. C a s e r e p o r t A 59-year-old woman presented at the neurology accumulation in the liver was proven with MRI, showing department with ataxia, involuntary movements and an iron concentration of 350 mmol/g (normal <36 mmol/g) mild cognitive impairment. Her medical history was according to the protocol of Gandon (University of Rennes, notable for chronic obstructive pulmonary disease and France) and liver biopsy (grade 4 iron accumulation).
    [Show full text]
  • Diagnosis and Treatment of Wilson Disease: an Update
    AASLD PRACTICE GUIDELINES Diagnosis and Treatment of Wilson Disease: An Update Eve A. Roberts1 and Michael L. Schilsky2 This guideline has been approved by the American Asso- efit versus risk) and level (assessing strength or certainty) ciation for the Study of Liver Diseases (AASLD) and rep- of evidence to be assigned and reported with each recom- resents the position of the association. mendation (Table 1, adapted from the American College of Cardiology and the American Heart Association Prac- Preamble tice Guidelines3,4). These recommendations provide a data-supported ap- proach to the diagnosis and treatment of patients with Introduction Wilson disease. They are based on the following: (1) for- Copper is an essential metal that is an important cofac- mal review and analysis of the recently-published world tor for many proteins. The average diet provides substan- literature on the topic including Medline search; (2) tial amounts of copper, typically 2-5 mg/day; the American College of Physicians Manual for Assessing recommended intake is 0.9 mg/day. Most dietary copper 1 Health Practices and Designing Practice Guidelines ; (3) ends up being excreted. Copper is absorbed by entero- guideline policies, including the AASLD Policy on the cytes mainly in the duodenum and proximal small intes- Development and Use of Practice Guidelines and the tine and transported in the portal circulation in American Gastroenterological Association Policy State- association with albumin and the amino acid histidine to 2 ment on Guidelines ; (4) the experience of the authors in the liver, where it is avidly removed from the circulation. the specified topic.
    [Show full text]
  • Practical Management of Iron Overload Disorder (IOD) in Black Rhinoceros (BR; Diceros Bicornis)
    animals Review Practical Management of Iron Overload Disorder (IOD) in Black Rhinoceros (BR; Diceros bicornis) Kathleen E. Sullivan, Natalie D. Mylniczenko , Steven E. Nelson Jr. , Brandy Coffin and Shana R. Lavin * Disney’s Animal Kingdom®, Animals, Science and Environment, Bay Lake, FL 32830, USA; [email protected] (K.E.S.); [email protected] (N.D.M.); [email protected] (S.E.N.J.); Brandy.Coffi[email protected] (B.C.) * Correspondence: [email protected]; Tel.: +1-407-938-1572 Received: 29 September 2020; Accepted: 26 October 2020; Published: 29 October 2020 Simple Summary: Black rhinoceros under human care are predisposed to Iron Overload Disorder that is unlike the hereditary condition seen in humans. We aim to address the black rhino caretaker community at multiple perspectives (keeper, curator, veterinarian, nutritionist, veterinary technician, and researcher) to describe approaches to Iron Overload Disorder in black rhinos and share learnings. This report includes sections on (1) background on how iron functions in comparative species and how Iron Overload Disorder appears to work in black rhinos, (2) practical recommendations for known diagnostics, (3) a brief review of current investigations on inflammatory and other potential biomarkers, (4) nutrition knowledge and advice as prevention, and (5) an overview of treatment options including information on chelation and details on performing large volume voluntary phlebotomy. The aim is to use evidence to support the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population. Abstract: Critically endangered black rhinoceros (BR) under human care are predisposed to non-hemochromatosis Iron Overload Disorder (IOD).
    [Show full text]
  • Iron Deficiency Anemia (IRIDA) • Rare
    Iron Deficiency: Review Melinda Wu, MD, MCR Oregon Health & Science University OHSU10/17/2019 Disclosure Information: a) Moderators/panelists/presenters: Melinda Wu has nothing to disclose. OHSUb) Funding sources: NIH/NHLBI- K08 HL133493 Objectives 1) To review iron body homeostasis 2) To review the etiologies of iron deficiency OHSU3) To review various treatment options of iron deficiency Part I: Review of Iron Body OHSUHomeostasis Iron Balance in the Body Iron is required for growth of all cells, not just hemoglobin! Heme proteins: cytochromes, catalase, peroxidase, cytochrome oxidase Flavoproteins: cytochrome C reductase, succinic dehydrogenase, NADH oxidase, xanthine oxidase Too little Too much Not enough for essential Accumulates in organs proteins: Promotes the formation of: • Hemoglobin • Oxygen radicals •OHSURibonucleotide reductase • Lipid peroxidation (DNA synthesis) • DNA damage • Cytochromes • Tissue fibrosis • Oxidases Iron Economy • The average adult has 4-5 g of body iron. • ~10% of dietary iron absorbed, exclusively in duodenum • Varies with: • Iron content of diet • Bioavailability of dietary iron • Iron stores in body • Erythropoietic demand • Hypoxia • Inflammation • More than half is incorporated into erythroid precursors/mature erythrocytes OHSU• Only ~1-2 mg of iron enters and leaves the body in a day on average. • About 1 mg of iron is lost daily in menstruating women. Lesjak, M.; K. S. Srai, S. Role of Dietary Flavonoids in Iron Homeostasis. Pharmaceuticals 2019 Systemic Iron Regulation: Absorption Iron status is regulated entirely at the level of absorption! • Heme iron (30-70%) > non-heme iron (<5%) • 2 stable oxidation states: Ferrous (Fe 2+) > Ferric (Fe 3+) • Elemental iron must be reduced to Fe2+ iron to be absorbed 1.
    [Show full text]
  • Ferriprox (Deferiprone) Tablets Contain 500 Mg Deferiprone (3-Hydroxy-1,2-Dimethylpyridin-4-One), a Synthetic, Orally Active, Iron-Chelating Agent
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use FERRIPROX safely and effectively. See full prescribing information for ------------------------------CONTRAINDICATIONS------------------------------- FERRIPROX. • Hypersensitivity to deferiprone or to any of the excipients in the FERRIPROX® (deferiprone) tablets, for oral use formulation. (4) Initial U.S. Approval: 2011 ------------------------WARNINGS AND PRECAUTIONS----------------------- WARNING: AGRANULOCYTOSIS/NEUTROPENIA • If infection occurs while on Ferriprox, interrupt therapy and monitor the See full prescribing information for complete boxed warning. ANC more frequently. (5.1) • Ferriprox can cause agranulocytosis that can lead to serious • Ferriprox can cause fetal harm. Women should be advised of the infections and death. Neutropenia may precede the development of potential hazard to the fetus and to avoid pregnancy while on this drug. agranulocytosis. (5.1) (5.3) • Measure the absolute neutrophil count (ANC) before starting Ferriprox and monitor the ANC weekly on therapy. (5.1) -----------------------------ADVERSE REACTIONS-------------------------------- • Interrupt Ferriprox if infection develops and monitor the ANC more frequently. (5.1) • The most common adverse reactions are (incidence ≥ 5%) chromaturia, • Advise patients taking Ferriprox to report immediately any nausea, vomiting and abdominal pain, alanine aminotransferase symptoms indicative of infection. (5.1) increased, arthralgia and neutropenia. (5.1, 6) -----------------------------INDICATIONS AND USAGE-------------------------- To report SUSPECTED ADVERSE REACTIONS, contact ApoPharma Inc. at: Telephone: 1-866-949-0995 FERRIPROX® (deferiprone) is an iron chelator indicated for the treatment of Email: [email protected] or FDA at 1-800-FDA-1088 or patients with transfusional iron overload due to thalassemia syndromes when www.fda.gov/medwatch current chelation therapy is inadequate. (1) Approval is based on a reduction in serum ferritin levels.
    [Show full text]
  • Mechanisms of Copper Deficiency in the Zebrafish Embryo Erik Madsen Washington University in St
    Washington University in St. Louis Washington University Open Scholarship All Theses and Dissertations (ETDs) January 2010 Mechanisms of Copper Deficiency in the Zebrafish Embryo Erik Madsen Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/etd Recommended Citation Madsen, Erik, "Mechanisms of Copper Deficiency in the Zebrafish Embryo" (2010). All Theses and Dissertations (ETDs). 220. https://openscholarship.wustl.edu/etd/220 This Dissertation is brought to you for free and open access by Washington University Open Scholarship. It has been accepted for inclusion in All Theses and Dissertations (ETDs) by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. WASHINGTON UNIVERSITY Division of Biology and Biomedical Sciences Molecular Cell Biology Dissertation Examination Committee Jonathan Gitlin, Chair John Atkinson Guojun Bu Aaron DiAntonio Steven Johnson Jeanne Nerbonne David Wilson MECHANISMS OF COPPER DEFICIENCY IN THE ZEBRAFISH EMBRYO by Erik Christian Madsen A dissertation presented to the Graduate School of Arts and Sciences of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2010 Saint Louis, Missouri ABSTRACT OF THE DISSERTATION Mechanisms of Copper Deficiency in the Zebrafish Embryo By Erik Christian Madsen Doctor of Philosophy in Biology and Biomedical Sciences (Molecular Cell Biology) Washington University in St. Louis, 2010 Professor Jonathan D. Gitlin, Chairperson Proper maternal nutrition is critical for early embryonic development. Despite overwhelming epidemiologic data indicating the benefits nutrient supplementation for the developing organism we do not fully understand the genetics of predisposition to abnormal developmental phenotypes when faced with suboptimal nutrient levels.
    [Show full text]