J. Fernandes· J.-M. Saudubray . G. Van den Berghe (Eds.): Inborn Metabolic Diseases Springer-Verlag Berlin Heidelberg GmbH J. Fernandes J.-M. Saudubray G. Van den Berghe (Eds.) Inborn Metabolic Diseases Diagnosis and Treatment 3rd, Revised Edition With 66 Figures and 57 Tables , Springer Dr. JOHN FERNANDES Professor Emeritus of Pediatrics Veldweg 87 8051 NP Hattem, The Netherlands Professor JEAN-MARIE SAUDUBRAY Hospital Necker-Enfants Malades 149 Rue de Sevres 75743 Paris Cedex 15, France Professor GEORGES VAN DEN BERGHE Christian de Duve Institute of Cellular Pathology Universite Catholique de Louvain Avenue Hippocrate 75 1200 Brussels, Belgium Cover Illustration: Putti by della Robbia at Spedale degli Innocenti, Firenze, Italy Library of Congress Cataloging in Publication Data applied for. Die Deutsche Bibliothek - CIP-Einheitsaufnahme Inborn metabolic diseases: diagnosis and treatment/I. Fernandes ... - 3., rev. ed. ISBN 978-3-662-04287-8 ISBN 978-3-662-04285-4 (eBook) DOI 10.1007/978-3-662-04285-4 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. 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-Verlag Berlin Heidelberg GmbH. Violations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 2000 Originally published by Springer-Verlag Berlin Heidelberg New York in 2000 Softcover reprint of the hardcover 3rd edition 2000 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting other relevant literature. Cover Design: Springer-Verlag, E. Kirchner Production: Pro Edit GmbH, 69126 Heidelberg, Germany Typesetting: Scientific Publishing Services (P) Ltd, Madras Printed on acid-free paper SPIN: 10708260 22/3134/goh - 5 4 3 2 1 0 Preface Five years have passed since the second edition of With respect to the contents of the book, most Inborn Metabolic Diseases; Diagnosis and Treatment chapters have been rewritten or extensively revised. A was published. The third edition, now being presented, few chapters from the second edition have been has been thoroughly updated and revised. Again, the deleted, since their contents are discussed in other clinical presentation, the methods to arrive at the chapters of the present edition. A few new chapters diagnosis and the treatment of the patient have have been introduced, such as a general chapter on remained the focus of the book, that for a large part treatment, which gives a comprehensive list of present has been written by clinicians for clinicians. The scope treatments and new trends, a chapter on persistent of the readership has enlarged: from the original teams hyperinsulinemic hypoglycemia, a combined chapter of pediatricians, biochemists and dieticians it now also on disorders of ketogenesis and ketolysis, a chapter on encompasses neurologists, internists, geneticists and disorders of proline and serine metabolism, a chapter psychosocial workers. This reflects the fact that for on disorders of cholesterol synthesis, and a chapter on many inborn metabolic diseases the survival of the defective leukotriene synthesis. For more detailed patients and their quality of life have improved. A information, particularly with respect to pathophysiol­ combination of facts has contributed to this: above all ogy and genetics, we recommend the eighth edition of refined methods for biochemical monitoring of the the Molecular and Metabolic Bases of Inherited Disease, condition of the patients, and treatments tailored to edited by Charles R. Scriver et al (Mc Graw-Hill, 2000). various stages of the disease and ages of the patients. In view of the rapidly expanding knowledge of Furthermore, refined molecular genetic investigation clinical, metabolic and genetic variability and their has uncovered not only a great heterogeneity of most influence on prognosis and treatment, it is important to metabolic disorders, but also contributed to genetic be aware of the existence of networks of experts and counselling. laboratories specialized in the diagnosis and treatment The book can be used in two main situations. When of inherited metabolic disorders. For countries of the the diagnosis is already suspected, the reader can go European Union such a list is compiled by the Society dir"ectly to the relevant chapter, which is always for the Study of Inborn Errors of Metabolism (SSIEM), presented in the design common to all chapters. for the United States and Canada, Japan and Australia However, when the diagnosis is unknown, the physi­ by the American, Japanese and Australian Societies of cian can first refer to Chapter 1, which presents Inherited Metabolic Diseases (SIMD, JIMD, and AIMD, symptoms according to four main entries: symptoms respectively) . in the newborn infant, acute symptoms of later onset The editors welcome new authors of old and new and recurrent attacks, chronic and general progressive chapters and pay tribute to the authors who, though symptoms, or symptoms related to an organ (system). not participating this time, laid the framework for this Each symptom can be found in the index list of the book. chapter, which refers either to the text, a table, a figure, an algorithm or a list of disorders, or a combination of John Fernandes these. From this introductory information it is easy to Jean-Marie Saudubray proceed to a relevant chapter in order to obtain more Spring 2000 Georges van den Berghe specific information. Contents Part I 13. Defects of the Respiratory Chain Diagnosis and Treatment: A. Munnich ................................ 157 General Principles 1. Clinical Approach to Inherited Metabolic Diseases Part IV J.-M. Saudubray, H. Ogier de Baulny, Disorders of Amino Acid Metabolism and C. Charpentier ......................... 3 and Transport 2. Diagnostic Procedures: 14. The Hyperphenylalaninaemias Function Tests and Postmortem Protocol I. Smith and P. Lee ......................... 171 J. Fernandes, J.-M. Saudubray, and J. Huber 43 15. Disorders of Tyrosine Metabolism 3. Emergency Treatments E.A. Kvittingen and E. Holme ................ 185 H. Ogier de Baulny and J.-M. Saudubray 53 16. Branched-Chain Organic Acidurias 4. Psychosocial Care of the Child and Family H. Ogier de Baulny and J.-M. Saudubray ....... 195 J.C. Harris ................................. 63 17. Disorders of the Urea Cycle 5. Treatment: Present Status and New Trends J.V. Leonard ............................... 213 J.H. Walter and J.E. Wraith .................. 75 18. Disorders of Sulfur Amino Acid Metabolism G. Andria, B. Fo",ler, and G. Sebastio 223 Part II Disorders of Carbohydrate Metabolism 19. Disorders of Ornithine and Creatine Metabolism 6. The Glycogen-Storage Diseases V.E. Shih and S. Stockler-Ipsiroglu ............ 233 J. Fernandes and G.P.A. Smit ................. 87 20. Disorders of Lysine Catabolism 7. Disorders of Galactose Metabolism and Related Cerebral Organic-Acid Disorders 103 R. Gitzelmann .............................. G.F. HoffInann ............................. 241 8. Disorders of Fructose Metabolism 21. Nonketotic Hyperglycinemia G. van den Berghe .......................... 111 K. Tada ................................... 255 9. Persistent Hyperinsulinemic Hypoglycemia 22. Disorders of Proline and Serine Metabolism P. de Lonlay and J.-M. Saudubray ............. 117 J. Jaeken .................................. 259 Part III 23. Transport Defects of Amino Acids Disorders of Mitochondrial Energy at the Cell Membrane: Cystinuria, Hartnup Metabolism Disease, and Lysinuric Protein Intolerance O. Simell, K. Parto, and K. Niinto-Salonen ...... 265 10. Disorders of Pyruvate Metabolism and the Tricarboxylic Acid Cycle D.S. Kerr, I.D. Wexler, and A.B. Zinn 127 Part V 11. Disorders of Fatty Acid Oxidation Vitamin-Responsive Disorders C.A. Stanley ............................... 139 24. Biotin-Responsive Multiple Carboxylase 12. Disorders of Ketogenesis and Ketolysis Deficiency A.A.M. Morris ............................. 151 E.R. Baumgartner and T. Suormala ............ 277 VIII Contents 25. Disorders of Cobalamin and Folate Transport Part IX and Metabolism Disorders of Metal Transport D.S. Rosenblatt ............................ 33. Copper Transport Disorders: Wilson Disease and Menkes Disease Part VI D.W. Cox and Z. Turner ..................... 385 Neurotransmitter and Small Peptide Disorders 34. Genetic Defects Related to Metals Other Than Copper 26. Disorders of N eurotransmission F. Jochum and 1. Lombeck ................... 393 J. Jaeken, C. Jakobs, and R. Weyers 301 27. Disorders in the Metabolism of Glutathione and Imidazole Dipeptides A. Larsson and J. Jaeken ..................... 313 Part X Organelle-Related Disorders: Part VII Lysosomes, Peroxisomes, and Golgi Disorders of Lipid and Bile Acid Metabolism and Pre-Golgi Systems 28. Dyslipidemias