DOCSLIB.ORG

Severe Megaloblastic Anemia: Vitamin Deficiency and Other Causes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Severe Megaloblastic Anemia: Vitamin Deficiency and Other Causes REVIEW CME MOC Daniel S. Socha, MD Sherwin I. DeSouza, MD Aron Flagg, MD Department of Laboratory Medicine, Department of Hematology and Medical Oncology, Department of Pediatric Hematology and Oncology, Robert J. Tomsich Pathology and Laboratory Taussig Cancer Institute, Cleveland Clinic Yale School of Medicine, New Haven, CT Medicine Institute, Cleveland Clinic Mikkael Sekeres, MD, MS Heesun J. Rogers, MD, PhD Department of Hematology and Medical Oncology and Department Department of Laboratory Medicine, Robert J. Tomsich Pathology and of Translational Hematology and Oncology Research, Taussig Laboratory Medicine Institute,Cleveland Clinic; Assistant Professor, Cancer Institute, Cleveland Clinic; Professor, Cleveland Clinic Lerner Cleveland Clinic Lerner College of Medicine of Case Western Reserve College of Medicine of Case Western Reserve, Cleveland, OH University, Cleveland, OH Severe megaloblastic anemia: Vitamin defi ciency and other causes ABSTRACT ot all megaloblastic anemias result N from vitamin defi ciency, but most do. De- Megaloblastic anemia causes macrocytic anemia from termining the underlying cause and initiating ineffective red blood cell production and intramedullary prompt treatment are critical, as prognosis and hemolysis. The most common causes are folate (vitamin management differ among the various condi- B9 ) defi ciency and cobalamin (vitamin B12) defi ciency. tions. Megaloblastic anemia can be diagnosed based on char- This article describes the pathobiology, acteristic morphologic and laboratory fi ndings. However, presentation, evaluation, and treatment of se- other benign and neoplastic diseases need to be con- vere megaloblastic anemia and its 2 most com- sidered, particularly in severe cases. Therapy involves mon causes: folate (vitamin B9) and cobalamin treating the underlying cause—eg, with vitamin supple- (vitamin B12) defi ciency, with 2 representative mentation in cases of defi ciency, or with discontinuation case studies. of a suspected medication. ■ MEGALOBLASTIC ANEMIA OVERVIEW KEY POINTS Megaloblastic anemia is caused by defec- The hallmark of megaloblastic anemia is macrocytic ane- tive DNA synthesis involving hematopoi- mia (mean corpuscular volume > 100 fL), often associ- etic precursors, resulting in ineffective red blood cell production (erythropoiesis) and ated with other cytopenias. intramedullary hemolysis. Macrocytic ane- mia with increased mean corpuscular vol- Dysplastic features may be present and can be diffi cult to ume (MCV), defi ned as more than 100 fL, differentiate from myelodysplastic syndrome. is the hallmark of megaloblastic anemia, but leukopenia and thrombocytopenia are also Megaloblastic anemia is most commonly caused by folate frequently present. defi ciency from dietary defi ciency, alcoholism, or malab- The incidence of macrocytosis is as high as 4% in the general population, but megalo- sorption syndromes or by vitamin B12 defi ciency, usually due to pernicious anemia. blastic anemia accounts for only a small frac- tion.1 Nonmegaloblastic causes of macrocytic anemia include ethanol abuse, myelodysplas- Both vitamin defi ciencies cause hematologic signs and tic syndrome, aplastic anemia, hypothyroid- 2,3 symptoms of anemia; vitamin B12 defi ciency also causes ism, liver disease, and drugs. Although these neurologic symptoms. causes are associated with increased MCV, they do not lead to the other features of mega- Oral supplementation is available for both vitamin loblastic anemia. The most frequent causes of megaloblastic defi ciencies; intramuscular vitamin B12 supplementa- tion should be used in cases involving severe neurologic anemia are defi ciencies of vitamin 9B (folate) or vitamin B (cobalamin) (Table 1). Less- symptoms or gastric or bowel resection. 12 frequent causes include congenital disorders doi:10.3949/ccjm.87a.19072 (inborn errors of metabolism), drugs (particu- CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 3 MARCH 2020 153 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. MEGALOBLASTIC ANEMIA TABLE 1 Characteristics of vitamin B12 vs folate defi ciency Vitamin B12 defi ciency Folate defi ciency Etiology Lack of intrinsic factor: pernicious anemia Dietary defi ciency: alcoholism, countries without food fortifi cation Malabsorption: celiac disease, prior gastric or ileal surgery Malabsorption: developed countries Dietary defi ciency less common Increased demand: pregnancy, hemolytic anemia, eczema Clinical Hematologic fi ndings: cytopenias Hematologic fi ndings: cytopenias presentation Neuropsychiatric symptoms: paresthesias, decreased proprioception and vibratory sense, dementia, confusion Evaluation Clinical history and physical examination: symptoms sec- Clinical history and physical examination: ondary to anemia and hemolysis, neurologic symptoms similar to vitamin B12 defi ciency, except no neurologic symptoms Laboratory testing: serum vitamin B12, methylmalonic acid, homocysteine, antiparietal cell and anti-intrinsic factor Laboratory testing: serum folate, red blood antibodies, serum gastrin cell folate, methylmalonic acid, homocysteine Gastric biopsy for suspected pernicious anemia Differential Other macrocytic anemias without megaloblastic features: Other macrocytic anemias without megalo- diagnosis liver disease, thyroid dysfunction, alcohol abuse blastic features: liver disease, thyroid dysfunc- tion, alcohol abuse Myelodysplastic syndrome, acute myeloid leukemia Myelodysplastic syndrome, acute myeloid Nitrous oxide exposure leukemia Medication effect Medication effect Treatment Parenteral vitamin B12 1–2 times per week until symptoms Oral folate daily improve, then monthly High-dose oral vitamin B12 daily Monitoring Clinical follow-up for improvement of neurologic symptoms Monitor hematologic response: and follow-up complete blood cell count Monitor hematologic response: complete blood cell count Pernicious anemia: consider monitoring methylmalonic acid larly chemotherapeutics and folate antago- Folate defi ciency has 3 main causes4,5: nists), micronutrient defi ciencies, and nitrous • Reduced intake from diets lacking folate oxide exposure.4,5 (rare in countries with vitamin fortifi cation) and alcoholism (see Case 1) ■ FOLATE DEFICIENCY • Decreased absorption from disorders affect- Folate is found in green leafy vegetables, fruits, ing nutrient absorption in the small bowel, nuts, eggs, and meats. Normal body stores of eg, celiac disease, infl ammatory bowel dis- folate are 5 to 30 mg. The recommended daily ease, and tropical sprue allowance depends on age, sex, and pregnancy • Increased demand from pregnancy, hemo- status, but is generally 400 μg in adults and lytic anemia, puberty, and eczematous con- 600 μg during pregnancy.6 ditions. 154 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 3 MARCH 2020 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. SOCHA AND COLLEAGUES ■ VITAMIN B12 DEFICIENCY TABLE 2 Vitamin B is produced by microorganisms 12 Causes of vitamin B defi ciency and is found almost exclusively in foods of 12 animal origin. Normal body stores of vitamin Common causes (related to malabsorption) B12 are 3 to 5 mg, and the recommended adult Autoimmune gastritis (pernicious anemia) daily intake is 2.4 μg.7,8 Celiac disease Causes of vitamin B12 defi ciency are listed in Table 2. Dietary defi ciency of vitamin B12 Infl ammatory bowel disease occurs less frequently than folate defi ciency because body stores can last for years owing Surgical gastrectomy, gastric bypass, ileal resection to effi cient enterohepatic recycling mecha- Less common causes nisms. Although uncommon, dietary B12 defi ciency can occur even in industrialized Nutritional countries in strict vegans and vegetarians, or (strict vegans, breastfed infants of mothers with vitamin B12 defi ciency) in breastfed infants of mothers with vitamin Nitrous oxide abuse B defi ciency. 12 Diphyllobothrium latum infection Complex absorption pathway Pancreatic insuffi ciency Dietary absorption of vitamin B12 is a complex process that begins with haptocorrin (also Drug effect (metformin, proton pump inhibitors) known as transcobalamin I or R-binder) pro- Inherited disorders affecting intrinsic factor or the cubam receptor duction by the salivary glands. Rare inherited disorder When food is digested in the stomach by (eg, methylmalonic acidemia, transcobalamin II defi ciency) gastric acid and pepsin, free vitamin B12 is re- leased and binds to haptocorrin.4,9 Information from references 4, 5, and 7. Simultaneously, gastric parietal cells se- crete intrinsic factor, which cannot interact Pernicious anemia Macrocytic with the vitamin B12-haptocorrin complex. and autoimmune gastritis Not until food moves into the duodenum, Chronic atrophic autoimmune gastritis is an anemia where trypsin and other pancreatic enzymes autoimmune process directed specifi cally at ei- with a mean cleave haptocorrin, is vitamin B free to 12 ther gastric parietal cells or intrinsic factor, or corpuscular bind to intrinsic factor.9 The resultant vi- both.10–12 Parietal cell damage leads to reduced tamin B12-intrinsic factor complex binds to production of gastric acid and intrinsic factor, volume > 100 fL the cubam receptor on the mucosal surface accompanied by a compensatory increase in is the hallmark of enterocytes in the ileum. From there, vi- serum gastrin levels. Decreased intrinsic fac- of megalo- tamin B12 is transported into the circulation tor leads to signifi cantly reduced absorption
Load more

Recommended publications
  • The Hematological Complications of Alcoholism
    The Hematological Complications of Alcoholism HAROLD S. BALLARD, M.D. Alcohol has numerous adverse effects on the various types of blood cells and their functions. For example, heavy alcohol consumption can cause generalized suppression of blood cell production and the production of structurally abnormal blood cell precursors that cannot mature into functional cells. Alcoholics frequently have defective red blood cells that are destroyed prematurely, possibly resulting in anemia. Alcohol also interferes with the production and function of white blood cells, especially those that defend the body against invading bacteria. Consequently, alcoholics frequently suffer from bacterial infections. Finally, alcohol adversely affects the platelets and other components of the blood-clotting system. Heavy alcohol consumption thus may increase the drinker’s risk of suffering a stroke. KEY WORDS: adverse drug effect; AODE (alcohol and other drug effects); blood function; cell growth and differentiation; erythrocytes; leukocytes; platelets; plasma proteins; bone marrow; anemia; blood coagulation; thrombocytopenia; fibrinolysis; macrophage; monocyte; stroke; bacterial disease; literature review eople who abuse alcohol1 are at both direct and indirect. The direct in the number and function of WBC’s risk for numerous alcohol-related consequences of excessive alcohol increases the drinker’s risk of serious Pmedical complications, includ- consumption include toxic effects on infection, and impaired platelet produc- ing those affecting the blood (i.e., the the bone marrow; the blood cell pre- tion and function interfere with blood cursors; and the mature red blood blood cells as well as proteins present clotting, leading to symptoms ranging in the blood plasma) and the bone cells (RBC’s), white blood cells from a simple nosebleed to bleeding in marrow, where the blood cells are (WBC’s), and platelets.
    [Show full text]
  • Detailed Investigations of Proximal Tubular Function in Imerslund-Grasbeck Syndrome
    Detailed investigations of proximal tubular function in Imerslund-Grasbeck syndrome. Tina Storm, Christina Zeitz, Olivier Cases, Sabine Amsellem, Pierre Verroust, Mette Madsen, Jean-François Benoist, Sandrine Passemard, Sophie Lebon, Iben Jønsson, et al. To cite this version: Tina Storm, Christina Zeitz, Olivier Cases, Sabine Amsellem, Pierre Verroust, et al.. Detailed in- vestigations of proximal tubular function in Imerslund-Grasbeck syndrome.. BMC Medical Genetics, BioMed Central, 2013, 14 (1), pp.111. 10.1186/1471-2350-14-111. inserm-00904107 HAL Id: inserm-00904107 https://www.hal.inserm.fr/inserm-00904107 Submitted on 13 Nov 2013 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Storm et al. BMC Medical Genetics 2013, 14:111 http://www.biomedcentral.com/1471-2350/14/111 RESEARCHARTICLE Open Access Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome Tina Storm1, Christina Zeitz2,3,4, Olivier Cases2,3,4, Sabine Amsellem2,3,4, Pierre J Verroust1,2,3,4, Mette Madsen1, Jean-François Benoist6, Sandrine Passemard7,8, Sophie Lebon8, Iben Møller Jønsson9, Francesco Emma10, Heidi Koldsø11, Jens Michael Hertz12, Rikke Nielsen1, Erik I Christensen1* and Renata Kozyraki2,3,4,5* Abstract Background: Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia.
    [Show full text]
  • Detailed Investigations of Proximal Tubular Function in Imerslund-Gräsbeck Syndrome
    Storm et al. BMC Medical Genetics 2013, 14:111 http://www.biomedcentral.com/1471-2350/14/111 RESEARCH ARTICLE Open Access Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome Tina Storm1, Christina Zeitz2,3,4, Olivier Cases2,3,4, Sabine Amsellem2,3,4, Pierre J Verroust1,2,3,4, Mette Madsen1, Jean-François Benoist6, Sandrine Passemard7,8, Sophie Lebon8, Iben Møller Jønsson9, Francesco Emma10, Heidi Koldsø11, Jens Michael Hertz12, Rikke Nielsen1, Erik I Christensen1* and Renata Kozyraki2,3,4,5* Abstract Background: Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia. IGS is caused by mutations in either of the genes encoding the intestinal intrinsic factor-vitamin B12 receptor complex, cubam. The cubam receptor proteins cubilin and amnionless are both expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers and lipoproteins. Consistent with this, low-molecular-weight proteinuria has been observed in most patients with IGS. The aim of this study was to characterise novel disease-causing mutations and correlate novel and previously reported mutations with the presence of low-molecular-weight proteinuria. Methods: Genetic screening was performed by direct sequencing of the CUBN and AMN genes and novel identified mutations were characterised by in silico and/or in vitro investigations. Urinary protein excretion was analysed by immunoblotting and high-resolution gel electrophoresis of collected urines from patients and healthy controls to determine renal phenotype.
    [Show full text]
  • AMN Directs Endocytosis of the Intrinsic Factor‐Vitamin B12
    Traffic 2010; 11: 706–720 © 2010 John Wiley & Sons A/S doi:10.1111/j.1600-0854.2010.01042.x AMN Directs Endocytosis of the Intrinsic Factor-Vitamin B12 Receptor Cubam by Engaging ARH or Dab2 Gitte Albinus Pedersen1,†, Souvik tubules of the kidney, cubam is involved in reabsorption Chakraborty2,†, Amie L. Steinhauser2, of various proteins from the glomerular ultrafiltrate (for 2 1,∗ example albumin, transferrin, apolipoprotein A-I and vita- Linton M. Traub and Mette Madsen min D-binding protein), thereby reducing proteinuria (5–8). The cubam complex has been shown to play an impor- 1 tant role during fetal development in rodents (2,4), but Department of Medical Biochemistry, University of presently its role in the human yolk sac is unclear. Aarhus, Ole Worms Alle,´ Bldg. 1170-1171, DK-8000 Aarhus C, Denmark ∼ 2Department of Cell Biology and Physiology, University of Cubilin is an 460-kDa protein composed of a short Pittsburgh School of Medicine, Pittsburgh, PA 15213, N-terminal region followed by eight epidermal growth USA factor (EGF)-like repeats and 27 contiguous CUB *Corresponding author: Mette Madsen, domains (9,10). The cubilin protein includes no identifiable [email protected] transmembrane region or classical signals for endocytosis. †These authors contributed equally to this study. These features are, however, found in the other cubam partner, AMN, which is an ∼45-kDa type I transmembrane Cubam is a multi-ligand receptor involved in dietary protein containing two putative internalization signals of uptake of intrinsic factor-vitamin B12 in the small intestine the FXNPXF type within its cytosolic domain (1,11,12).
    [Show full text]
  • ©Ferrata Storti Foundation
    550 scientific correspondence trophoresis. The patients’ mean age was 51.7±20.1 years (range The characteristics of megaloblastic anemia associated 23-89 years). We also randomly selected age-matched subjects with thalassemia with complete enough data to rule out any complicated condi- tions to fit the criteria of the other 3 groups. Group B contained 10 patients with uncomplicated megaloblastic anemia. Group C Combined megaloblastic anemia with thalassemia is easily contained 12 patients with uncomplicated thalassemia minor masked because of the loss of macrocytosis. We performed a without any previous transfusion. Group D contained 11 healthy retrospective study to compare the major parameters in 4 controls without any history of anemia and with normal CBC and groups of subjects in order to show the characteristics of vitamin levels. Mann-Whitney’s U test was used to test the sig- patients with megaloblastic anemia and thalassemia. Group A nificance of each main parameter. comprised 9 patients with megaloblastic anemia and tha- Table 1 shows the various parameters in the 4 groups of sub- lassemia, group B comprised 10 patients with uncomplicated jects. There was no age difference between groups. The MCV in megaloblastic anemia. Group C comprised 12 uncomplicated group A patients with megaloblastic anemia and thalassemia thalassemia trait and group D was formed of 11 healthy con- was not significantly different from that in the normal subjects, trols. The mean corpuscolar volume (MCV) in group A patients but was significantly lower and higher than that in patients with was not significantly different from that in normal subjects, megaloblastic anemia and with thalassemia, respectively.
    [Show full text]
  • Chapter 03- Diseases of the Blood and Certain Disorders Involving The
    Chapter 3 Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (D50- D89) Excludes2: autoimmune disease (systemic) NOS (M35.9) certain conditions originating in the perinatal period (P00-P96) complications of pregnancy, childbirth and the puerperium (O00-O9A) congenital malformations, deformations and chromosomal abnormalities (Q00-Q99) endocrine, nutritional and metabolic diseases (E00-E88) human immunodeficiency virus [HIV] disease (B20) injury, poisoning and certain other consequences of external causes (S00-T88) neoplasms (C00-D49) symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (R00-R94) This chapter contains the following blocks: D50-D53 Nutritional anemias D55-D59 Hemolytic anemias D60-D64 Aplastic and other anemias and other bone marrow failure syndromes D65-D69 Coagulation defects, purpura and other hemorrhagic conditions D70-D77 Other disorders of blood and blood-forming organs D78 Intraoperative and postprocedural complications of the spleen D80-D89 Certain disorders involving the immune mechanism Nutritional anemias (D50-D53) D50 Iron deficiency anemia Includes: asiderotic anemia hypochromic anemia D50.0 Iron deficiency anemia secondary to blood loss (chronic) Posthemorrhagic anemia (chronic) Excludes1: acute posthemorrhagic anemia (D62) congenital anemia from fetal blood loss (P61.3) D50.1 Sideropenic dysphagia Kelly-Paterson syndrome Plummer-Vinson syndrome D50.8 Other iron deficiency anemias Iron deficiency anemia due to inadequate dietary
    [Show full text]
  • The Path to an Orally Administered Protein Therapeutic for the Treatment of Diabetes Mellitus
    Syracuse University SURFACE Chemistry - Dissertations College of Arts and Sciences 12-2012 The Path to an Orally Administered Protein Therapeutic for the Treatment of Diabetes Mellitus Susan Clardy James Syracuse University Follow this and additional works at: https://surface.syr.edu/che_etd Part of the Chemistry Commons Recommended Citation James, Susan Clardy, "The Path to an Orally Administered Protein Therapeutic for the Treatment of Diabetes Mellitus" (2012). Chemistry - Dissertations. 196. https://surface.syr.edu/che_etd/196 This Dissertation is brought to you for free and open access by the College of Arts and Sciences at SURFACE. It has been accepted for inclusion in Chemistry - Dissertations by an authorized administrator of SURFACE. For more information, please contact [email protected]. Abstract Protein therapeutics like insulin and glucagon-like peptide-1 analogues are currently used as injectable medications for the treatment of diabetes mellitus. An orally administered protein therapeutic is predicted to increase patient adherence to medication and bring a patient closer to metabolic norms through direct effects on hepatic glucose production. The major problem facing oral delivery of protein therapeutics is gastrointestinal tract hydrolysis/proteolysis and the inability to passage the enterocyte. Herein we report the potential use of vitamin B12 for the oral delivery of protein therapeutics. We first investigated the ability of insulin to accommodate the attachment of B12 at the B1 vs. B29 amino acid position. The insulinotropic profile of both conjugates was evaluated in streptozotocin induced diabetic rats. Oral administration of the conjugates produced significant drops in blood glucose levels, compared to an orally administered insulin control, but no significant difference was observed between conjugates.
    [Show full text]
  • General Refugee Health Guidelines
    GENERAL REFUGEE HEALTH GUIDELINES U.S. Department of Health and Human Services Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Division of Global Migration and Quarantine August 6, 2012 Background On average, more than 50,000 refugees relocate to the United States annually. 1 They come from diverse regions of the world and bring with them health risks and diseases common to all refugee populations as well as some that may be unique to specific populations. The purpose of this document is to describe general and optional testing components that do not fall into the specific disease categories of these guidelines. These guidelines are based upon principles of best practices, with references to primary published reports when available. This document differs from others in the guidelines, which recommend screening for specific disorders. The guidelines in this document include testing for abnormalities or clinical conditions that are not specific disorders but are suggestive of underlying disorders. The tests in this document may indicate either acute or chronic disorders and generally indicate the need for further testing and evaluation to identify the condition causing the abnormality. Testing for chronic health conditions is important, since these conditions are common in newly arriving refugees, both children and adults. 2 Since refugee populations are diverse and are predisposed to diseases that may differ from those found in the U.S. population, the differential diagnosis and initial evaluation of abnormalities are discussed to assist the clinician. General and Optional Tests Many disorders may be detected by using general, nonspecific testing modalities.
    [Show full text]
  • Genetic Heterogeneity of Megaloblastic Anaemia Type 1 in Tunisian Patients
    J Hum Genet (2007) 52:262–270 DOI 10.1007/s10038-007-0110-0 ORIGINAL ARTICLE Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients Chiraz Bouchlaka Æ Chokri Maktouf Æ Bahri Mahjoub Æ Abdelkarim Ayadi Æ M. Tahar Sfar Æ Mahbouba Sioud Æ Neji Gueddich Æ Zouheir Belhadjali Æ Ahmed Rebaı¨ Æ Sonia Abdelhak Æ Koussay Dellagi Received: 2 August 2006 / Accepted: 21 December 2006 / Published online: 7 February 2007 Ó The Japan Society of Human Genetics and Springer 2007 Abstract Megaloblastic anaemia 1 (MGA1) is a rare geneous and can be caused by mutations in either the autosomal recessive condition characterized by selec- cubilin (CUBN) or the amnionless (AMN) gene. In tive intestinal vitamin B12 malabsorption and pro- the present study we investigated the molecular defect teinuria. More than 200 MGA1 patients have been underlying MGA1 in nine Tunisian patients belonging identified worldwide, but the disease is relatively to six unrelated consanguineous families. Haplotype prevalent in Finland, Norway and several Eastern and linkage analyses, using microsatellite markers Mediterranean regions. MGA1 is genetically hetero- surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these fami- C. Bouchlaka Á C. Maktouf Á S. Abdelhak (&) lies were screened for the Finnish, Mediterranean and Molecular Investigation of Genetic Orphan Diseases, Arabian mutations already published. None of the Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, screened mutations could be detected in our popula- Tunis Belve´de`re, Tunisia tion. One family showed a linkage to AMN gene.
    [Show full text]
  • Cubam Receptor-Mediated Endocytosis in Hindgut-Derived Pseudoplacenta of A
    bioRxiv preprint doi: https://doi.org/10.1101/2021.02.01.429082; this version posted May 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Title 2 Cubam receptor-mediated endocytosis in hindgut-derived pseudoplacenta of a 3 viviparous teleost Xenotoca eiseni 4 5 Running title 6 Endocytosis in pseudoplacenta of teleost 7 8 Authors 9 Atsuo Iida1, *, Kaori Sano2, Mayu Inokuchi3, Jumpei Nomura1, Takayuki Suzuki1, Mao 10 Kuriki4, Maina Sogabe4, Daichi Susaki5, Kaoru Tonosaki5, Tetsu Kinoshita5, Eiichi 11 Hondo1 12 13 Affiliations 14 1. Department of Animal Sciences, Graduate School of Bioagricultural Sciences, 15 Nagoya University, Tokai National Higher Education and Research System, Nagoya, 16 Aichi, Japan. 17 2. Department of Chemistry, Faculty of Science, Josai University, Sakado, Saitama, 18 Japan. 19 3. Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, 20 University of Tokyo, Bunkyo, Tokyo, Japan 21 4. Department of Regeneration Science and Engineering, Institute for Frontier Life and 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.01.429082; this version posted May 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 22 Medical Sciences, Kyoto University, Kyoto, Kyoto, Japan. 23 5. Kihara Institute for Biological Research, Yokohama City University, Yokohama, 24 Kanagawa, Japan. 25 26 Correspondence: Atsuo Iida 27 E-mail: [email protected] 28 29 Keywords 30 endocytosis, Goodeidae, proteolysis, pseudoplacenta, teleost, viviparity 31 32 Summary statement 33 Here, we report that an endocytic pathway is a candidate for nutrient absorption in 34 pseudoplacenta of a viviparous teleost.
    [Show full text]
  • Structural and Functional Characterisation of the Cobalamin Transport Protein Haptocorrin
    Research Collection Doctoral Thesis Structural and functional characterisation of the cobalamin transport protein haptocorrin Author(s): Furger, Evelyne Publication Date: 2012 Permanent Link: https://doi.org/10.3929/ethz-a-007608480 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library DISS ETH 20838 Structural and Functional Characterisation of the Cobalamin Transport Protein Haptocorrin A dissertation submitted to ETH ZURICH for the degree of DOCTOR OF SCIENCES Presented by EVELYNE FURGER MSc ETH Pharm. Sci. Born 25.04.1981 Citizen of Silenen UR Accepted on the recommendation of Prof. Dr. Roger Schibli, examiner Prof. Dr. Ebba Nexø, co-examiner Prof. Dr. Simon M. Ametamey, co-examiner 2012 To my parents Acknowledgements I would like to express my gratitude to all those who supported me to complete this thesis. First and foremost, I owe my deepest gratitude to my supervisor Dr. Eliane Fischer whose help, encouragement and stimulating enthusiasm helped me through all the times of the dissertation. Furthermore, I want to thank all my colleagues from the Center of Radiopharmaceutical Sciences at the ETH Zurich and the Paul Scherrer Institute in Villigen for all their help, support and the nice time we spent together inside and outside the lab. I would like to thank Prof. Roger Schibli for giving me the opportunity to perform my doctorate in his group and Prof. Ebba Nexø and Prof. Simon M. Ametamey for being in the committee as co-referees. Finally, I want to express my heartfelt gratitude to my parents Eduard and Marianna, Carmen, Patricia, Thomas, Nicole and all my friends for their never-ending support and care.
    [Show full text]
  • Novel Compound Heterozygous Mutations in AMN Cause Imerslund-Gräsbeck Syndrome in Two Half-Sisters: a Case Report Emma Montgomery1, John A
    Montgomery et al. BMC Medical Genetics (2015) 16:35 DOI 10.1186/s12881-015-0181-2 CASE REPORT Open Access Novel compound heterozygous mutations in AMN cause Imerslund-Gräsbeck syndrome in two half-sisters: a case report Emma Montgomery1, John A. Sayer1,2*, Laura A. Baines1, Ann Marie Hynes2, Virginia Vega-Warner3, Sally Johnson4, Judith A. Goodship2 and Edgar A. Otto3 Abstract Background: Imerslund-Gräsbeck Syndrome (IGS) is a rare autosomal recessive disease characterized by intestinal vitamin B12 malabsorption. Clinical features include megaloblastic anemia, recurrent infections, failure to thrive, and proteinuria. Recessive mutations in cubilin (CUBN) and in amnionless (AMN) have been shown to cause IGS. To date, there are only about 300 cases described worldwide with only 37 different mutations found in CUBN and 30 different in the AMN gene. Case presentation: We collected pedigree structure, clinical data, and DNA samples from 2 Caucasian English half-sisters with IGS. Molecular diagnostics was performed by direct Sanger sequencing of all 62 exons of the CUBN gene and 12 exons of the AMN gene. Because of lack of parental DNA, cloning, and sequencing of multiple plasmid clones was performed to assess the allele of identified mutations. Genetic characterization revealed 2 novel compound heterozygous AMN mutationsinbothhalf-sisterswithIGS.Trans-configuration of the mutations was confirmed. Conclusion: We have identified novel compound heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Gräsbeck Syndrome. Keywords: Amnionless, Cobalamin deficiency, Anemia, Proteinuria, Vitamin B12, Mutation screening Background in AMN, encoding amnionless were found [5]. Since then, Imerslund-Gräsbeck Syndrome (IGS) is a rare autosomal many additional genetically confirmed cases have been re- recessive disorder characterized by intestinal cobalamin ported with about 300 IGS cases published worldwide [6].
    [Show full text]