Physician’s Guide to the Treatment and Follow-Up of Metabolic Diseases Nenad Blau · Georg F. Hoffmann James Leonard · Joe T. R. Clarke (Eds.) Physician’s Guide to the Treatment and Follow-Up of Metabolic Diseases Foreword by C. R. Scriver With 12 Figures and 267 Tables 123 Nenad Blau Georg F. Hoffmann Division of Clinical Chemistry Universitätsklinik für Kinder- and Biochemistry und Jugendmedizin University Children’s Hospital Im Neuenheimer Feld 150 Steinwiesstrasse 75 D-69120 Heidelberg 8032 Zurich Germany Switzerland e-mail: e-mail: [email protected] Georg_Hoffmann @med.uni-heidelberg.de James Leonard Joe T. R. Clarke Biochemistry, Endocrinology Division of Clinical and Metabolism Unit & Metabolic Genetics Institute of Child Health Hospital for Sick Children 30, Guilford Street 555 University Avenue London, WC1N 1EH Toronto, Ontario, M5G 1X8 UK Canada e-mail: [email protected] e-mail: [email protected] Library of Congress Control Number: 2004110452 ISBN-10 3-540-22954-X Springer-Verlag Berlin Heidelberg New York ISBN-13 978-3-540-22954-4 Springer-Verlag Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole or part of the mate- rial is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. 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Editor: Gabriele Schröder, Heidelberg, Germany Desk Editor: Irmela Bohn, Germany Production: ProEdit GmbH, Heidelberg, Germany Cover: Frido Steinen-Broo, EStudio Calamar, Spain Typesetting: LE-TEX, Jelonek, Schmidt & Vöckler GbR, Leipzig, Germany Printed on acid-free paper 24/3151ML 543210 Foreword The greatest difficulty in life is to make knowledge effective, to convert it into practical wisdom. Sir William Osler. The inborn errors of metabolism, as a group of metabolic diseases, are rela- tively rare and are sometimes called “orphan diseases.”As a group, they account for about 1 in 2,500 births (Applegarth et al. 2000) and, as a cumulative group reaching 20 years of age, their prevalence is about 40 cases per 100,000 popula- tion. In terms of patient days of continuous supervision and care, hundreds of thousands of such days are involved per generation of these patients. Although experience with these diseases as a class may be small and people expert in their management may be relatively few, in the years to come many caregivers will become involved. This book offers help to them. Until the mid-twentieth century, hereditary metabolic and other genetic diseases were considered to be purely “genetic” problems. Destiny would take its course, treatment did not exist, and genetic counseling about recurrence risks was virtually all that could be offered. Phenylketonuria (PKU) was then shown to be a treatable genetic disease in which early diagnosis and effective treatment prevented the disease (mental retardation) in PKU. Other genetic diseases for which an environmental experience was an essential component of cause (e. g., exposure to a dietary component or a drug) were then seen to yield to treatment. Combinations of early diagnosis and access to treat- ment began to change our outlook. Accordingly, diagnosis is the natural focus of our companion book (The Physician’s Guide to the Laboratory Diagnosis of Metabolic Disease); the present volume focuses on treatment and follow- up. Over the past two decades, systematic analyses of treatment outcomes for genetic disease have been attempted (Hayes et al. 1985; Treacy et al. 1995, 2001). There has been slow but significant progress overall, reflecting improvements in treatment protocols, in the therapeutic agents (drugs and foods, for example), in tissue transplantation, and in enzyme replacement by other means. Now there is another problem. Patients with treatable hereditary metabolic disease grow up and become adult-age subjects. For them, treatment continues but under new auspices. The net result is an ever-growing community of persons in need of continuing care (Lee 2002, 2003). This book also addresses that challenge. VI Foreword The Physician’s Guide to the Treatment and Follow-up of Metabolic Disease is not an in-depth reference resource such as may be found elsewhere. This new book is concise, its information is succinct, and it describes procedures of as- sistance to patients in need of continuous care and support. Approximately 300 different disorders are identified for which a documented therapeutic modality is available. How to monitor the therapeutic effect is described. One of the legacies of the Human Genome Project is ignorance; we know so little about our genome and how it works. On the other hand, the project is a significant beginning of new knowledge from which new forms of treatment, to neutralize the effect of mutant disease-causing alleles, will emerge. Accordingly one can anticipate a long life for The Physician’s Guide to the Treatment and Follow-up of Metabolic Disease as it evolves and incorporates new information, knowledge, and wisdom. CharlesR.Scriver,MDCMFRS AlvaProfessorEmeritusofHumanGenetics.McGillUniversity References 1. Applegarth DA, Toone JR, Lowry RB (2000) Incidence of inborn errors of metabolism in British Columbia, 1969–1996. Pediatrics 105:1–6 2. Hayes A, Costa T, Scriver CR, Childs B (1985) The effect of Mendelian disease on human health. II. Response to treatment. Amer J Med Genet 21:243–255 3. Lee PJ (2002) Growing older. The adult metabolic clinic. J Inher Metab Dis 25:252–260 4. Lee PJ (2003) The adult patient with hereditary metabolic disease. In: Scriver CR et al. (eds) The metabolic and molecular bases of inherited disease (online). McGraw Hill, New York.(External update in Chap. 5. Treatment of genetic disease) 5. Treacy E, Childs B, Scriver CR (1995) Response to treatment in hereditary metabolic disease: 1993 survey and ten year comparison. Am J Hum Genet 56:359–367 6. Treacy EP, Valle D, Scriver CR (2001) The treatment of genetic disease. In: Scriver CR et al. (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw Hill, New York, pp 175–191 Preface You may ask whether there is a need for another book about metabolic dis- orders. Although there are a number of good books dealing with both the diagnosis and treatment of inborn errors of metabolism, many of them are rather complex and detailed. This book starts where the previous one, Physi- cian’s Guide to the Laboratory Diagnosis of Metabolic Diseases, leaves off: what to do after the laboratory reports arrive, and how to proceed once the final diagnosis is made. In contrast to diagnostic procedures, which are today fairly straightforward, treatment and follow-up of inherited metabolic disorders are more complex. Appropriate treatment depends not only on the exact diagnosis, but the management may differ from one country to another to meet local circumstances. This book is divided into two parts: the first part deals with initial manage- ment (emergency treatment of hypoglycemia, hyperammonemia, ketoacidosis, lactic acidemia, liver failure, acute encephalopathy, effect of anesthesia) while awaiting final diagnosis; the second part describes the treatment of groups of disorders. Each chapters starts with a list of disorders, which are numbered thesamewayasinthefirstbook,Physician’s Guide to the Laboratory Diagno- sis of Metabolic Diseases, followed by simple protocols for the treatment and follow-up. Although this book reflects as much as possible current knowledge of the treatment of inherited metabolic disorders, written by experts in this field, medicine is constantly advancing. The application of this information in daily practice remains the responsibility of the attending physician. The details have been checked, but the authors, editors, and publisher can take no responsibility for any consequences arising from the application of the information in the management of any patients. Drug doses, particularly those used rarely, should always be checked meticulously. Nenad Blau GeorgF.Hoffmann James Leonard JoeT.R.Clarke List of Contributors Generoso Andria Jörgen Bierau Dipartimento di Pediatria Academic Hospital Maastricht Università Federico II Department of Clinical Genetics Via S. Pansini 5 Laboratory for Genetic Metabolic Diseases 80131 Napoli 3-X Building Italy PO Box 2500 e-mail: [email protected] 6202 AZ Maastricht The Netherlands Bruce A. Barshop e-mail: [email protected] UCSD Biochemical Genetics Department of Pediatrics Nenad Blau La Jolla, CA 92093 Division of Clinical Chemistry and Biochemistry USA University Children’s Hospital e-mail: [email protected] Steinwiesstrasse 75 8032 Zurich Roberta Battini Switzerland Division of Child Neurology and Psychiatry e-mail: [email protected] University of Pisa Stella Maris Scientific Institute Carolien Boelen Via dei Giacinti 1 University Medical Center Sint Radboud 56018 Calambrone, Pisa CAKN Italy Huispostnummer 435 e-mail: [email protected] Geert Grooteplein 10 PO Box 9101 Anna Biason-Lauber 6500 HB Nijmegen Dept. of Pediatrics The Netherlands Division of Clinical Chemistry and Biochemistry e-mail: [email protected] and Endocrinology/Diabetology University of Zurich Steinwiesstrasse 75 8032 Zurich Switzerland e-mail: [email protected] X List of Contributors Peter Burgard Tom J.