Terryn Thesis.Indb

Total Page:16

File Type:pdf, Size:1020Kb

Terryn Thesis.Indb Ghent University Faculty of Medicine and Health Sciences Department of Internal Medicine Nephrology Division Screening for Fabry disease indications, methods and implications Wim Terryn Thesis submitted in fulfilment of the requirements for the degree of Doctor in Medical Sciences 2013 Promotors: prof. dr. Raymond Vanholder prof. dr. Bruce Poppe Faculteit Geneeskunde en Gezondheidswetenschappen Departement Interne Geneeskunde Divisie Nefrologie Screening voor de Ziekte van Fabry indicaties, methoden en implicaties Wim Terryn Proefschrift voorgelegd tot het behalen van de graad van Doctor in de Medische Wetenschappen 2013 Promotoren: prof. dr. Raymond Vanholder prof. dr. Bruce Poppe Promotors Prof. dr. Raymond Vanholder Ghent University, Faculty of Medicine and Health Sciences Department of Internal Medicine, Nephrology Division Prof. dr. Bruce Poppe Ghent University, Faculty of Medicine and Health Sciences Center for Medical Genetics Members of the examination committee Prof. dr. Elfriede Debaere Universiteit Gent, België Prof. dr. Linda De Meirleir Vrije Universiteit Brussel, België Prof. dr. Olivier Devuyst Universität Zürich, Switserland Dr. Gabor Linthorst Universiteit van Amsterdam, Nederland Prof. dr. Koen Pameleire Universiteit Gent, België Prof. dr. Rudy Van Coster Universiteit Gent, België Prof. dr. Koen Vandewoude Universiteit Gent, België © Wim Terryn Screening for Fabry disease: indications, methods and implications / W. Terryn Universiteit Gent, Campus UZ Gent, De Pintelaan 185, 9000 Gent Thesis Universiteit Gent 2013 – with summary in Dutch and French Lay-out, cover & figures: Dirk De Weerdt (www.ddwdesign.be) General Table of Contents Chapter 1 7 The Place of Fabry Disease among the Sphingolipidoses and Inborn Errors of Metabolism Chapter 2 49 Screening for Fabry Disease in High-Risk Populations Chapter 3 85 Attenuated Fabry Disease Chapter 4 99 Screening and Treatment in Chronic Kidney Disease Chapter 5 123 General Discussion and Perspectives Appendix: Population Screening: Problems associated with the detection of atypical or unknown variants and presentation of a possible solution 131 Summary 137 Samenvatting 141 Résumé 145 Curriculum Vitae 149 Woorden van dank 153 6 Chapter 1 1 The Place of Fabry Disease among the Sphingolipidoses and Inborn Errors of Metabolism Chapter 1: Contents Preface 9 Introduction 11 Metabolism 11 Inborn errors of metabolism: from black urine to gene alterations 11 The lysosome is the stomach of the cell 13 In lysosomal storage disorders, an enzyme deficiency causes storage of intermediary degradation products 14 The clinical presentation of LSDs is extremely variable 16 Sphingolipidoses are lysosomal storage disorders caused by accumulation of sphingolipid degradation products 17 Fabry disease: Case Study 27 A short review on Fabry disease 28 Epidemiology 29 Clinical description 29 Determination of enzyme activity is the gold standard for diagnosis of Fabry disease in males 34 In females, mutation analysis should confirm a clinical suspicion of Fabry disease 34 Mutation detection and mutation scanning 36 Fabry disease has a wide phenotypical spectrum, a low genotype-phenotype correlation and is difficult to recognize 37 Conventional medical treatment of Fabry disease 37 Enzyme replacement therapy in Fabry disease 38 Case study: Discussion 38 Conclusion 39 Aims and Outlines of this thesis 40 References 42 Fabry disease among the sphingolipidosis and inborn errors of metabolism PREFACE abry disease is a rare X-linked progressive multisystem disorder that belongs to the group of lysosomal storage disorders (LSDs). Signs and symptoms of Fabry disease Fmay be first noted in childhood, such as acroparesthesia, heat intolerance, the in- ability to sweat and micro-albuminuria. However, because physicians often do not attribute these signs and symptoms to Fabry disease, patients may not be diagnosed until adulthood, when cerebrovascular disease, cardiac hypertrophy and progressive kidney disease can oc- cur. Fabry disease manifests itself not only in males but also in heterozygotes. Heterozy- gous females show a more variable and in general a more attenuated course. Nonetheless, the mean life expectancy is significantly shortened in both sexes albeit more prominent in males than in females. The name “Fabry disease” originates from the 19th century. In Fabry patients, angiokera- tomas, which are small purplish skin lesions, progressively appear on the skin and were first described in 1898 by two independently working physicians, William Anderson and Johannes Fabry (Figure 1.1.) 1. Figure 1.1. Johannes Fabry. “Ein beitrag zur Kenntniss der Purpura haemorrhagica nodularis” (Purpura papulosa haemorrhagica Hebrae) 1898. 9 Chapter 1 In the late 1950s and early 1960s, de Duve and colleagues identified the lysosome as a cellular organelle responsible for intracellular digestion and recycling of macromolecules. This was the scientific breakthrough that would lead to the understanding of the physiolog- ical basis of the LSDs. Pompe disease was the first disease to be identified as a LSDs in 1963 2.The deficiency of α-Galactosidase was first shown to be the enzymatic defect in Fabry disease in 1967 by Brady and colleagues using radiolabelled globotriaosylceramide (Gb-3), which is accumulated in Fabry disease 3. Subsequently, Kint from the Ghent University dem- onstrated that α-Galactosidase could act on the synthetic substrates (p-nitrophenyl–α-d- galactoside and 4-methylumbelliferyl–α-d-galactoside) and was specific for the α-anomeric galactosidic linkage 4. This breakthrough eventually facilitated the diagnosis of Fabry dis- ease. 10 Fabry disease among the sphingolipidosis and inborn errors of metabolism INTRODUCTION n inborn errors of metabolism (IEMs), a defect in a protein that functions as enzyme, co- factor or transport protein leads to the accumulation or the deficiency of a metabolite. IMost of these deficiencies concern one single protein. They can be classified according to the general type of metabolism or the specific cellular organelle that is involved. Classes of IEMs concern the metabolism of amino acids, organic acids, carbohydrates, fatty acids, metals, or are due to deficiencies in lysosomal or peroxisomal enzymes. Most IEMs are very rare, but as a group, they are common. The symptoms of IEMS are extremely diverse, and can be almost any presenting complaint, especially in children, ranging from growth failure and skin rashes to immunodeficiency, vomiting and hyperventilation. Owing primarily to advances in diagnostic technology, a rapidly growing list of IEM presenting in adulthood is emerging. Some of these, e.g. Scheie disease, are caused by are milder variants of the same enzyme deficiency that commonly causes death in childhood. Others, such as clas- sical hemochromatosis, almost never present in childhood. Fabry disease belongs to the sphingolipidoses, which are a group of LSDs, where a defective activity of a lysosomal pro- tein results in intra-lysosomal accumulation of undegraded metabolites. In the first part of this chapter, a short introduction to the IEMs is presented with more details on the sphingolipidoses. Metabolism In all cells of living organisms, a set of chemical reactions, called “metabolism” enables growth, reproduction, maintenance of structure, and response to the environment. The term metabolism is derived from the Greek “μεταβολη”, which means “change”: a chemi- cal reaction takes place where substance 1 is being transformed into substance 2, because substance 1 has to be degraded or because substance 2 has to be generated. In multicel- lular organisms, enzymes mediate a significant number of these chemical reactions. These are large biological molecules that catalyse or increase the rate of the chemical reaction. In case of IEMs, changes in the genes that encode for an enzyme disable the chemical reac- tion, resulting either in the accumulation of substance 1 or in a deficiency of substance 2. (Figure 1.2.) Inborn errors of metabolism: from black urine to gene alterations Alkaptonuria or “black urine disease” is a key example of how IEMs shaped our current understanding of these rare diseases 5. It was the first IEM described in 1902 by Sir Archibald Garod. This disease was much later fully described as the result of a defect in the hepatic en- zyme homogentisate 1,2 –deoxygenase (encoded by the HGD gene) which participates in the degradation of the amino-acid tyrosine. As a result, a toxic tyrosine degradation product 11 Chapter 1 Figure 1.2. Inborn errors of metabolism: a mutation in the gene that codes for an enzyme results in the accu- mulation of substance 1 or the deficiency of substance 2. homogentisic acid or alkapton accumulates and is excreted in the urine in large quantities. This causes damage to cartilage (resulting in osteoarthritis, especially causing low back pain at young age) and heart valves and precipitates as kidney stones. Homogentisic acid, when exposed to air, colours black staining the sclera and urine of these patients. Since 1902, hundreds of IEM have been described and can be classified according to the concerning defective metabolic pathway or cellular organelle , Presentation is usually in the neonatal period but can occur at any time, even in adult- hood. In older children and adolescents, an IEM should be considered in case of subtle neurologic or psychiatric abnormalities. Many of these patients who have been diagnosed with “birth injury”, atypical psychiatric disorders or medical diseases like multiple sclerosis,
Recommended publications
  • Neuroradiologic Findings in Fucosidosis, a Rare Lysosomal Storage Disease
    Neuroradiologic Findings in Fucosidosis, a Rare Lysosomal Storage Disease James M. Provenzale, Daniel P. Barboriak, and Katherine Sims Summary: Fucosidosis is a rare lysosomal storage disorder with vacuolated secondary lysosomes containing some fine the clinical features of mental retardation, cardiomegaly, dysos- fibrillar material and lamellated membrane structures. tosis multiplex, progressive neurologic deterioration, and early A magnetic resonance (MR) examination at the age of death. The neuroradiologic findings in two patients are reported, 10 years showed confluent regions of hyperintense signal and include abnormalities within the globus pallidus (both pa- on T2-weighted images in the periventricular regions, tients) and periventricular white matter (one patient). most prominent surrounding the atria of the lateral ventri- cles. Hyperintense signal was noted in the globus pallidus Index terms: Brain, metabolism; Degenerative disease, Pediatric on T1-weighted images, with corresponding hypointense neuroradiology signal on T2-weighted images (Fig 1). Fucosidosis is a rare metabolic disorder caused by decreased amounts of the enzyme Case 2 a-L-fucosidase, which results in the accumula- A 2-year-old boy was examined for speech delay and tion of fucose-rich storage products within psychomotor retardation. He was born at term after a many organs, including the brain. Patients with normal pregnancy, and appropriate development oc- this disorder usually have delayed intellectual curred during the first year of life. However, by age 2 years, and motor development, and often die within the patient had not developed speech, exhibited autistic the first decade of life. Computed tomographic behavior, and performed motor tasks poorly. Physical ex- (CT) findings have been reported in a few cases amination findings included coarsened facial features, nar- (1, 2).
    [Show full text]
  • Childhood Dementia Initiative
    Childhood Dementia in Australia: quantifying the burden on patients, carers, the healthcare system and our society Prepared by: Dominic Tilden, Madeline Valeri and Magda Ellis THEMA Consulting Pty Ltd www.thema.net Prepared for: Childhood Dementia Initiative www.childhooddementia.org THEMA Consulting Report (2020). Childhood Dementia in Australia: quantifying the burden on patients, carers, the healthcare system and our society. www.childhooddementia.org/burdenstudy Released on the 18th November 2020 Sydney, Australia. © Childhood Dementia Initiative 2020 Website address for further details. www.childhooddementia.org KEY POINTS : Childhood dementia is a recognised, albeit little known group of disorders, comprised of more than 70 individual genetic conditions. : Childhooddementiadisordersareprogressiveanddevastatinginnatureandposeasignificantlycomplex medicalchallenge,withpatientstypicallyrelyingonfulltimesupportivecareandextensivehealthcare services in the mid-later stages of the disease. : ThisstudydemonstratesforthefirsttimetheburdenassociatedwithchildhooddementiainAustralia, the tremendous negative impact it has on affected children, families and the community, and the resulting economic costs. : Effective therapeutic intervention remains an unmet clinical need for the vast majority of childhood dementia disorders. : It is estimated that the collective incidence of disorders that cause childhood dementia is 36 per 100,000 live births. This equates to 129 births in Australia each year. : In 2021, it is estimated there will be 2273 Australians
    [Show full text]
  • Geting Processes
    Translational Science of Rare Diseases 4 (2019) 133–157 133 DOI 10.3233/TRD-190047 IOS Press Practical management of lysosomal storage disorders (LSDs) Pranoot Tanpaiboona,b,∗ aAdvanced Diagnostics Genetics, Genomics and R&D, Quest Diagnostics, San Juan Capistrano, CA, USA bChildren’s National Rare Disease Institute, Michigan Ave NW, Washington, DC, USA Abstract. Lysosomal Storage Disorders (LSDs) comprise a group of disorders causing defects at the organelle and sub- organelle level with a wide range of pathophysiologies and clinical consequences. Signs and symptoms of LSDs involve multiple organ systems. The main pathological mechanism of most LSDs was previously thought to be cytotoxic effects of a specific storage substance secondary to functional impairment or insufficient lysosomal enzymes. Other pathophysiologic mechanisms of LSDs have been discovered such as dysfunction of cell signaling, disturbance of cell homeostasis, inflamma- tory process and dysfunction of autophagy. The goal of treatment is to balance equilibrium of the enzyme and the accumulated substance. Replacing deficient enzyme through exogenous enzyme replacement therapy (ERT) or stem cell transplantation has been the main method of treatment for several years. The ability of ERT to alleviate neurologic symptoms is limited owing to the inability of the exogenous enzyme to cross the blood-brain barrier. The benefit of stem cell transplantation on neurologic symptoms has been demonstrated for Hurler syndrome, but it is not clear for most LSDs. Other strategies, such as gene therapy, have been under development to overcome this limitation and provide a better outcome. Early treatment or pre-symptomatic treatment could also slow disease progression and improve prognosis.
    [Show full text]
  • 4Th Glycoproteinoses International Conference Advances in Pathogenesis and Therapy
    Program & Abstracts 4TH GLYCOPROTEINOSES INTERNATIONAL CONFERENCE ADVANCES IN PATHOGENESIS AND THERAPY ISMRD ST. LOUIS, MISSOURI, UNITED STATES Program & Abstracts I SM R D ADVANCES IN PATHOGENESIS AND THERAPY Program & Abstracts ISMRD would like to say A Very Special Thank You to the following organizations and companies who have very generously given donations and sponsorship to support the 4th International Conference on Glycoproteinoses THE PRENILLE EDWARD MALLINCKRODT FOUNDATION JR FOUNDATION MARK HASKINS I SM R D 4TH GLYCOPROTEINOSES INTERNATIONAL CONFERENCE 2015 ADVANCES IN PATHOGENESIS AND THERAPY Program & Abstracts ISMRD is very proud to display 10 featured Expression of Hope artworks to be Auctioned at the Gala Dinner. These beautiful prints are from Genzyme’s featured Artwork selection. Contents Welcome 1 SCIENTIFIC COMMITTEE: Stuart Kornfeld ISMRD Mission & Governance 3 (Chair, Scientifi c Planning Committee) Steve Walkley Sara Cathey ISMRD General Information 5 Richard Steet Sean Thomas Ackley, Philippines Miriam Storchli, Switzerland Alessandra d’Azzo ‘Hope’ by Sarah Noble, New Zealand Scientifi c Program 9 FAMILY CONFERENCE COMMITTEE: Family Program for Mucolipidosis 11 Jenny Noble (Conference Organiser) Jackie James (Conference Organiser Family Program For Alpha Mannosidosis /Sialidosis/ 13 - St. Louis) Fucosidosis/Aspartylglucosaminuria Mark Stark John Forman ‘All around the world’ by Zih Yun Li , Taiwan Childrens Program 16 Susan Kester Carolyn Paisley-Dew Tish Adkins Abstracts 17 Sara DeAngelis, Russia Gayle Rose, United States Speaker Profi les 60 Delegates 81 Helen Walker, Australia Nicklas Harkins, Canada Naomi Arai, Japan David Wentworth, Serbia I SM R D 4TH GLYCOPROTEINOSES INTERNATIONAL CONFERENCE 2015 ADVANCES IN PATHOGENESIS AND THERAPY Program & Abstracts On behalf of the Scientifi c Planning Committee, I want to extend a warm welcome to all the investigators and Welcome! families who have traveled to St.
    [Show full text]
  • DIAGNOSIS and THERAPIES for MUCOPOLYSACCHARIDOSES by Francyne Kubaski a Dissertation Submitted to the Faculty of the University
    DIAGNOSIS AND THERAPIES FOR MUCOPOLYSACCHARIDOSES by Francyne Kubaski A dissertation submitted to the Faculty of the University of Delaware in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biological Sciences Spring 2017 © 2017 Francyne Kubaski All Rights Reserved DIAGNOSIS AND THERAPIES FOR MUCOPOLYSACCHARIDOSES by Francyne Kubaski Approved: __________________________________________________________ Robin W. Morgan, Ph.D. Chair of the Department of Biological Sciences Approved: __________________________________________________________ George H. Watson, Ph.D. Dean of the College of Arts and Sciences Approved: __________________________________________________________ Ann L. Ardis, Ph.D. Senior Vice Provost for Graduate and Professional Education I certify that I have read this dissertation and that in my opinion it meets the academic and professional standard required by the University as a dissertation for the degree of Doctor of Philosophy. Signed: __________________________________________________________ Erica M. Selva, Ph.D. Professor in charge of dissertation I certify that I have read this dissertation and that in my opinion it meets the academic and professional standard required by the University as a dissertation for the degree of Doctor of Philosophy. Signed: __________________________________________________________ Shunji Tomatsu, Ph.D. Member of dissertation committee I certify that I have read this dissertation and that in my opinion it meets the academic and professional standard required by the University as a dissertation for the degree of Doctor of Philosophy. Signed: __________________________________________________________ Robert W. Mason, Ph.D. Member of dissertation committee I certify that I have read this dissertation and that in my opinion it meets the academic and professional standard required by the University as a dissertation for the degree of Doctor of Philosophy.
    [Show full text]
  • International Conference
    5TH GLYCOPROTEINOSES INTERNATIONAL CONFERENCE Rome, Italy November 1-4 2017 EMBRACING INNOVATION ADVANCING THE CURE PROGRAM & ABSTRACTS 5TH GLYCOPROTEINOSES INTERNATIONAL CONFERENCE ROME, ITALY NOVEMBER 1-4 2017 EMBRACING INNOVATION ADVANCING THE CURE ISMRD would like to say a very special thank you to the following organizations and companies who have very generously given donations to support the 5th International Conference on Glycoproteinoses. ISMRD is an internationally focused not-for-profi t organization whose mission is to advocate for families and patients aff ected by one of the following disorders. Alpha-Mannosidosis THE WAGNER FOUNDATION Aspartylglucosaminuria Beta-Mannosidosis Fucosidosis Galactosialidosis ISMRD is very grateful for all the help and support that Symposia has given us Sialidosis (Mucolipidosis I) in the organization of our Conference on-the-ground support in Rome. Mucolipidosis II, II/III, III alpha/beta Mucolipidosis III Gamma Schindler Disease EMBRACING INNOVATION ADVANCING THE CURE SCIENTIFIC COMMITTEE: Alessandra d’Azzo CHAIR Contents Amelia Morrone Italy Richard Steet USA Welcome 2 Heather Flanagan-Steet USA ISMRD Mission & Governance 4 Dag Malm Norway ISMRD General Information 6 Thomas Braulke Dedicated to helping patients Germany in the rare disease community Stuart Kornfeld with unmet medical needs Scientifi c Program 10 USA Ultragenyx Pharmaceutical Inc. is a clinical-stage Family Program 14 ISMRD CONFERENCE biopharmaceutical company committed to creating new COMMITTEE: therapeutics to combat serious,
    [Show full text]
  • Early Clinical Signs in Lysosomal Diseases
    Rare Diseases Meeting Proceedings Early clinical signs in lysosomal diseases Camelia Alkhzouz1,2, Diana Miclea1,2, Simona Bucerzan1,2, Cecilia Lazea1,2, Ioana Nascu2, Paula Grigorescu Sido2 1) Iuliu Hatieganu University of Abstract Medicine and Pharmacy, Cluj-Napoca, Background and aim. The lysosomal storage diseases are a group of monogenic Romania diseases with multisystemic impairment and chronic progression induced by the 2) Center of Expertise for Rare deficiency of lysosomal acid hydrolases involved in the breakdown of various Diseases Lysosomal Diseases, Clinical macromolecules. The accumulation occurs in the macrophages of the reticule- Emergency Hospital for Children, Cluj, endothelial system and causes enlargement and functional impairment. The mainly Romania involved organs are the brain, liver, spleen, bones, joints, airways, lungs, and heart. The aim of this study was to evaluate early symptoms, signs and the delay in the diagnosis of different lysosomal diseases. Methods. The medical documentation of 188 patients with lysosomal storage disorders, aged 1-70 years, were analyzed. All these patients were specifically diagnosed, by enzyme and molecular assay. Results. The age of clinical signs onset varies in different type of lysosomal diseases, from the first months of life or early childhood in severe form, to adulthood in attenuated forms. The delay between the clinical signs onset and specific diagnosis ranged from 0.5 months to 57.91 years. Conclusions. The lysosomal storage diseases are rare diseases with childhood onset,
    [Show full text]
  • Childhood Dementia Initiative
    the case for urgent action “Childhood dementia. The fact that these two words go together is appalling. We need to recognise this as a serious and urgent issue and fix it.” Sean Murray, Director, Childhood Dementia Initiative Childhood Dementia Initiative (2020). Childhood Dementia: the case for urgent action. www.childhooddementia.org/whitepaper Released on the 18th November 2020 Sydney, Australia. © Childhood Dementia Initiative 2020 Website address for further details. www.childhooddementia.org 3 Today, there are an estimated 700,000 children and young people living with dementia worldwide. Their short lives will be shaped by progressive brain damage, social isolation, pain and suffering. Many will not live into adulthood, some will die in their infant years. With less than 5% of all identified conditions that lead to childhood dementia having a treatment, it is time to transform the way we approach therapy development and management of these disorders. Children are dying, we need to act; fast. In 2013, following the shock diagnosis of both of my children with Sanfilippo Syndrome, a condition that causes childhood dementia, I started the Sanfilippo Children’s Foundation. In the 7 years that followed, we raised over $9 million towards our cause and transformed funding and management of Sanfilippo research in Australia; the work of the Foundation continues. But during this time I was continuously and consistently dismayed watching small, often family-run foundations around the world all struggling to raise funds and drive research. Researchers, although well-intentioned, were also severely underfunded, and incentives or imperatives for research to be undertaken across multiple disorders with similar presentation were non-existent.
    [Show full text]
  • Eira Kelo | Kelo | 156 | Eira
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE dissertations provided by UEF Electronic Publications | 156 | Eira| 156 Kelo | Eira Kelo Catalytic and Therapeutic Characteristics of Human Aspartylglycosaminuria (AGU), Recombinant Glycosylasparaginase an inherited lysosomal storage Catalytic and Therapeutic Characteristics Human of Recombinant Glycosylasparaginase and Bacterial L-asparaginases Eira Kelo disease, is caused by the deficient and Bacterial L-asparaginases activity of a lysosomal enzyme glycosylasparaginase (GA). Catalytic and Therapeutic Loss of GA activity results in the Characteristics of Human accumulation of glycoasparagines in tissues leading to progressive Recombinant Glycosylasparaginase psychomotor retardation and a shortened life span. Currently there is no cure for and Bacterial L-asparaginases AGU. In this study, the effectiveness of enzyme replacement therapy (ERT) with human recombinant GA was evaluated in the mouse model of AGU. Furthermore, the enzymatic properties of GA and bacterial asparaginases were compared. This study reveals new therapeutic and catalytic properties of human GA and bacterial asparaginases. Publications of the University of Eastern Finland Dissertations in Health Sciences Publications of the University of Eastern Finland Dissertations in Health Sciences isbn 978-952-61-1045-5 EIRA KELO EIRA KELO Catalytic and therapeutic characteristics of Catalytic and therapeutic characteristics of human recombinant glycosylasparaginase human recombinant glycosylasparaginase
    [Show full text]
  • Invitasjon Til Å Foreslå Nye Medlemmer I Bioteknologirådet
    Til Legeforeningen her Oslo, 16.07.2018 Høring- Invitasjon til å foreslå nye medlemmer i Bioteknologirådet Styret i PSL har behandlet saken og vil i den anledning foreslå som nye medlemmer i Bioteknologirådet: styremedlem Dag Malm og medlem Even Holt CV for begge de foreslåtte kandidatene følger vedlagt (se de påfølgende sider). For styret i Praktiserende spesialisters landsforening /PSL Frøydis Olafsen leder Praktiserende spesialisters landsforening • Postboks 1152 Sentrum • NO-0107 Oslo Besøksadresse: Legenes hus • Akersgt. 2 Telefon: +47 23 10 90 00 • Faks: +47 23 10 91 50 • Bankgiro 5074.09.95615 CURRICULUM VITAE Updated: Jan 15th 2017 Dr. med. Dag MALM (Last name Jacobsen until 021085), Born July 1th 1953 in Tromsø, Norway: Citizenship: Norwegian Civil status: Married Children: 3 (Range 25-33 years, Mean 28 years) Languages spoken: Scandinavian, English and German (fluently). French and Spanish (poorly). Education: University Qualifying Examination, Kongsbakken College, Tromsø, 1971. Final Examination in Medicine, University of Göttingen, Germany 1977 (2.part) and 1978 (Final part). Norwegian Additional Examination at the Universitety of Oslo mars 1976. License to practice as a Medical Doctor: Spring 1978 (Germany) and 1980 (Norway). Specialist in internal medicine 1985. Specialist in digestive tract disorders (Gastroenterology, Hepatology and Endoscopy combined) 1990. Doctoral Degree 1995 on the topic "Studies on the intracellular regulation of insulin secretion in pancreatic islets: An experimental study with special reference to the effect of cholecystokinin, somatostatin, and galanin on the hydrolysis of phosphatidyl inositol." Service in hospitals: - District General Hospital Alfeld, Germany, Dept. Surgery, Intern 020577-310777 3 months. - District General Hospital Alfeld, Germany, Dept. Medicine, Intern 010877-301177 4 months.
    [Show full text]
  • Our Mission and Vision CONTENTS • President's Piece
    ISMRD, a 501 © not-for-profit organization, FEIN 53-2164838 | website www.ismrd.org Our Mission and Vision https://www.facebook.com/groups/ 82945687520/ ISMRD is the leading advocate for families world-wide affected by Glycoprotein Storage Diseases. https://twitter.com/ISMRD Through partnerships built with medicine, science and industry Donations This we seek to detect and cure these diseases, and to provide a global network of support and information. ISMRD is a 501(c) charitable organisation based in the United States serving a global constituency. We provide We seek a future in which children with Glycoprotein Storage our services, which include our newsletter, website, Disease can be detected early, treated effectively and go on to outreach activities and support of research, without live long, healthy and productive lives. requesting monthly dues or any other financial restrictions. We gratefully accept donations that will ISMRD supports the following disorders enable us to continue toward our goal of a future free of the tragic consequences of Glycoprotein Storage Diseases. Alpha Mannosidosis, Aspartylglucosaminuria, Beta Mannosidosis, Fucosidosis, Galactosialidosis, Mucolipidosis II alpha/beta (I-Cell Donations can be made via our website using Disease), Mucolipidosis III alpha/beta (Pseudo-Hurler Polydystrophy), Mucolipidosis III Gamma, Schindler Disease and Sialidosis ISMRD Board of Directors CONTENTS President's Piece President Jackie James Treasurer Mark Stark Blessing from the Pope Vice President, Administration Jenny Noble
    [Show full text]
  • Allogeneic Hematopoietic Cell Transplantation for Genetic Diseases and Acquired Anemias
    MEDICAL POLICY POLICY TITLE ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR GENETIC DISEASES AND ACQUIRED ANEMIAS POLICY NUMBER MP-9.055 Original Issue Date (Created): 10/1/2014 Most Recent Review Date (Revised): 2/24/2021 Effective Date: 8/1/2021 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY I. POLICY Allogeneic hematopoietic cell transplantation is considered medically necessary for select patients with the following disorders: Hemoglobinopathies Sickle cell anemia for children or young adults with either a history of prior stroke or at increased risk of stroke or end-organ damage. Homozygous β -thalassemia (i.e., thalassemia major Bone marrow failure syndromes Aplastic anemia including hereditary (including Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond, Diamond-Blackfan) or acquired (e.g., secondary to drug or toxin exposure) forms. Primary immunodeficiencies Absent or defective T cell function (e.g., severe combined immunodeficiency, Wiskott- Aldrich syndrome, X-linked lymphoproliferative syndrome) Absent or defective natural killer function (e.g. Chediak-Higashi syndrome) Absent or defective neutrophil function (e.g. Kostmann syndrome, chronic granulomatous disease, leukocyte adhesion defect) (See Policy Guideline # 1.) Inherited metabolic disease Lysosomal and peroxisomal storage disorders except Hunter, Sanfilippo, and Morquio syndromes (See Policy Guideline # 2) Page 1 MEDICAL POLICY POLICY TITLE ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR GENETIC DISEASES AND ACQUIRED ANEMIAS POLICY NUMBER MP-9.055 Genetic disorders affecting skeletal tissue Infantile malignant osteopetrosis (Albers-Schonberg disease or marble bone disease) POLICY GUIDELINES Guideline 1 The following lists the immunodeficiencies that have been successfully treated by allogeneic hematopoietic cell transplantation (allo-HCT) (Gennery & Cant et al, 2008).
    [Show full text]