Table Of ContentNutrition
Management
of Inherited Metabolic
Diseases
Lessons from Metabolic
University
Laurie E. Bernstein
Fran Rohr
Sandy van Calcar
Editors
Second Edition
123
Nutrition Management of Inherited
Metabolic Diseases
Laurie E. Bernstein • Fran Rohr
Sandy van Calcar
Editors
Nutrition Management
of Inherited Metabolic
Diseases
Lessons from Metabolic University
Second Edition
Editors
Laurie E. Bernstein Fran Rohr
Children’s Hospital Colorado Met Ed Co
University of Colorado Hospital Boulder, CO, USA
Aurora, CO, USA
Sandy van Calcar
Molecular and Medical Genetics
Oregon Health & Science University
Portland, OR, USA
ISBN 978-3-030-94509-1 ISBN 978-3-030-94510-7 (eBook)
https://doi.org/10.1007/978-3-030-94510-7
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Preface
Nutrition Management of Inherited Metabolic Diseases: Lessons from
Metabolic University is dedicated to the nutrition management of patients
with inherited metabolic diseases (IMD). It presents a compilation of topics
that have been taught at Metabolic University (MU), an interactive, didactic
educational program that has trained over 1000 metabolic dietitians/nutri-
tionists, physicians, genetic counselors, and nurses since 2006. The purpose
of MU, and thus the subject matter included within, is intended to assist the
entry-level clinician with a broad understanding of the nutrition management
of inherited metabolic diseases.
Each chapter in the book reflects both the author’s literature review and
insights from their clinical experience. For many disorders there is no con-
sensus in the literature regarding the nutritional management, likely because
the incidence of IMD is low and randomized clinical trials on intervention
strategies are rare. In addition, each disorder has a wide spectrum of disease
severity. Recognizing that there are variations in practice, the precept of MU
is that nutrition management of IMD is not a “cookbook.” Rather, the key to
management lies in understanding how the inactivity of an enzyme in a meta-
bolic pathway determines which components of the diet must be restricted
and which must be supplemented, as well as the monitoring of appropriate
biomarkers to make diet adjustments and ensure the goals of therapy are met.
The goals of nutrition therapy are to correct the metabolic imbalance to lower
the risk of morbidity and mortality associated with the disorder and to pro-
mote normal growth and development by providing adequate nutrition.
Readers are encouraged to confer with their clinical teams regarding manage-
ment protocols specific to their institutions and to recognize that management
of metabolic disease is complex and guidance provided in the book may not
apply to every clinical situation.
This book contains mostly subject matter covered at MU and in general
the chapters are authored by the experts who presented the material. Therefore,
it is not a comprehensive treatise on IMD, but rather a textbook on the most
frequently encountered challenges in IMD nutrition. The book contains intro-
ductory chapters on nutrition and metabolism principles common to many
metabolic disorders and disease-specific chapters on disorders of amino acid,
fat, and carbohydrate metabolism.
Feedback from MU participants regarding the efficacy and effectiveness
of MU confirmed that they attended MU primarily to obtain practical guid-
v
vi Preface
ance on nutrition management for their IMD patients. Therefore, each
nutrition chapter in the book highlights principles of nutrition management,
how to initiate a diet, and biomarkers to monitor the diet. Diet calculations
are another element of MU that appears at the end of each nutrition chapter.
The book is designed for day-to-day clinical use. We hope it proves help-
ful in the nutrition management of your patients with inborn errors of
metabolism.
Disclaimer
The authors, editors, and publishers have made every effort to provide accu-
rate information. However, they are not responsible for errors, omissions, or
for any outcomes related to the use of the contents of this book and take no
responsibility for the use of the products and procedures described. The infor-
mation presented within this book is based on training, knowledge of medi-
cine, biochemistry, nutrition, genetics, and the clinical experience of the
authors. Medical and nutrition management of patients with inborn errors of
metabolism varies between individuals and between management teams. The
information presented within this book represents one way, among many, to
manage a patient. If questions arise pertaining to the individual management
of a patient with whom you are involved, it is best to discuss issues and alter-
native ideas with your medical team.
Aurora, CO, USA Laurie E. Bernstein
Boulder, CO, USA Fran Rohr
Portland, OR, USA Sandy van Calcar
Acknowledgments
We would like to thank BioMarin Pharmaceutical, Inc. and Nutricia North
America for support of Metabolic University.
We acknowledge Amanda Hamm, Morgan Drumm, DTR; and Sommer
Gaughan, RD, for their contributions in bringing this book to fruition.
And to those who inspire and teach us:
• Phyllis Acosta, DrPH, RD, for her lifelong contributions to this field and
to her mentorship
• Stephen Goodman, MD, PhD, for his lifelong contributions to this field
and his mentorship
• Our colleagues in metabolism at Boston Children’s Hospital, the University
of Colorado/Children’s Hospital Colorado, the University of Wisconsin-
Madison/Waisman Center, and Oregon Health & Science University
• Our patients
vii
Contents
Part I Background
1 Introduction to Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Janell Kierstein
2 Newborn Screening for Inherited Metabolic Diseases . . . . . . . . . 23
Erica Wright
3 Pathophysiology of Inherited Metabolic Diseases . . . . . . . . . . . . 33
Peter R. Baker II
4 Metabolic Intoxication Syndrome in a Newborn . . . . . . . . . . . . . 45
Maria Giżewska
5 Anabolism: Practical Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Kimberly A. Kripps and Johan L. K. Van Hove
6 Protein Requirements in Inherited Metabolic Diseases . . . . . . . 65
Steven Yannicelli
7 Laboratory Evaluations in Inherited Metabolic Diseases . . . . . . 85
Curtis R. Coughlin II
8 Gene Therapy for Inherited Metabolic Diseases . . . . . . . . . . . . . 97
Nicola Longo and Kent Lai
Part II Aminoacidopathies
9 Phenylketonuria: Phenylalanine Neurotoxicity . . . . . . . . . . . . . . 113
Maria Giżewska
10 Nutrition Management of Phenylketonuria . . . . . . . . . . . . . . . . . 127
Sandy van Calcar
11 Medical and Nutrition Management of Phenylketonuria:
Pegvaliase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Nicola Longo, Ashley Andrews, and Fran Rohr
12 Nutrition Management of Maternal Metabolic Disorders . . . . . 169
Fran Rohr and Sandy van Calcar
ix
x Contents
13 Hereditary Tyrosinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Austin Larson
14 Homocystinuria and Cobalamin Disorders . . . . . . . . . . . . . . . . . 197
Janet A. Thomas
15 Nutrition Management of Homocystinuria and Cobalamin
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Ann-Marie Roberts
16 Nutrition Management of Urea Cycle Disorders . . . . . . . . . . . . . 225
Erin MacLeod
17 Nutrition Management of Maple Syrup Urine Disease . . . . . . . . 241
Sandy van Calcar
Part III Organic Acidemias
18 Organic Acidemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Janet A. Thomas
19 Glutaric Acidemia Type I: Diagnosis and Management . . . . . . . 277
Curtis R. Coughlin II
20 Nutrition Management of Glutaric Acidemia Type 1 . . . . . . . . . 285
Laurie E. Bernstein
21 Nutrition Management of Propionic Acidemia and
Methylmalonic Acidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
Mary Sowa
Part IV F atty Acid Oxidation Disorders
22 Fatty Acid Oxidation Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Curtis R. Coughlin II
23 Nutrition Management of Fatty Acid Oxidation Disorders . . . . 325
Fran Rohr
Part V Disorders of Carbohydrate Metabolism
24 Nutrition Management of Galactosemia . . . . . . . . . . . . . . . . . . . . 339
Laurie E. Bernstein and Sandy van Calcar
25 Glycogen Storage Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Aditi Korlimarla, Rebecca Gibson, and Priya S. Kishnani
26 Nutrition Management of Glycogen Storage Disease . . . . . . . . . 363
Mary Sowa
Appendix A. Nutrient Composition of Frequently Used
Parenteral Fluids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Appendix B. Maintenance Fluid Requirements . . . . . . . . . . . . . . . . . . 379
Contents xi
Appendix C. Energy Needs Required for Anabolism During
Acute Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Appendix D. Dietary Reference Intakes . . . . . . . . . . . . . . . . . . . . . . . . 383
Appendix E. Carnitine in Inherited Metabolic Diseases . . . . . . . . . . . 389
Appendix F. Quick Guide to Acylcarnitine Profiles . . . . . . . . . . . . . . . 393
Appendix G. Simplified Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
Appendix H. Interpreting Quantitative Fatty Acid Profiles . . . . . . . . 397
Appendix I. Calculation of Glucose Infusion Rate and Cornstarch
Dosing for Patients with Glycogen Storage Disease . . . . . . . . . . . . . . . 401
Appendix J. Guide to Counting Carbohydrates for Patients with
GSD Type 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
Appendix K: At-A-Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
