Nutrition Management of Inherited Metabolic Diseases: Lessons from Metabolic University

Description

This text presents a compilation of topics that have been taught at Metabolic University (MU), an interactive, didactic educational program that has trained over 600 metabolic dietitians/nutritionists, physicians, nurses and genetic counselors. This book was created in 2014 for the metabolic community. The 1st edition contains only subject matter covered at Metabolic University; therefore, it is not a comprehensive treatise on Inherited Metabolic Disorders (IMD) but rather a text on the most frequently encountered challenges in IMD nutrition. Each chapter in the book highlights principles of nutrition management, how to initiate a diet, and biomarkers to monitor the diet. Recognizing that there are variations in practice, this book addresses that the key to management lies in the understanding how the inactivity of an enzyme in a metabolic 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 2nd edition is an updated and more extensive version covering the nutrition management of IMD, and covers a wide range of these disorders, including phenylketonuria and other aminoacidopathies, organic acidemias, urea cycle disorders, fatty acid oxidation disorders, galactosemia and glycogen storage diseases. Guidance is also provided on laboratory evaluations and biochemical testing and monitoring. Topics such as newborn screening for IMD, as well as nutrition management during pregnancy and transplantation, are also addressed. In addition, current medical management therapies is included. Preface Disclaimer Acknowledgments Contents Contributors Part I: Background 1: Introduction to Genetics 1.1 Background 1.2 From Genes to Proteins 1.3 Genetic Variants 1.3.1 Variant Effects on Gene Structure 1.3.2 Variant Effects on Amino Acid Sequence 1.3.3 Variant Effects on the Protein 1.4 Variant Nomenclature 1.5 Genetic Testing 1.5.1 Genetic Testing Technologies 1.5.2 Interpretation of Genetic Testing 1.5.3 Purposes of Genetic Testing 1.6 Genotype and Phenotype 1.7 Single Gene Inheritance Patterns and Pedigrees 1.7.1 Single Gene Inheritance Patterns 1.7.2 Pedigrees 1.8 Summary References 2: Newborn Screening for Inherited Metabolic Diseases 2.1 Background 2.2 Newborn Screening by Tandem Mass Spectrometry 2.3 Standardization of Newborn Screening 2.4 The Newborn Screening Process 2.5 Limitations of Newborn Screening 2.5.1 Disorders That Present Early in Life 2.5.2 Disorders That Have Risk of False Negatives 2.5.3 Metabolic Disorders Not Included on Newborn Screening 2.6 Future of Newborn Screening References 3: Pathophysiology of Inherited Metabolic Diseases 3.1 Background 3.2 Pathophysiology of Organs 3.2.1 The Liver 3.2.2 The Muscle 3.2.3 The Kidney 3.2.4 The Brain References 4: Metabolic Intoxication Syndrome in a Newborn 4.1 Background 4.2 Classification 4.2.1 Disorders Presenting with Intoxication Syndrome 4.2.2 Disorders of Reduced Tolerance to Fasting 4.2.3 Disorders of Mitochondrial Energy Metabolism 4.2.4 Disorders of Neurotransmission 4.2.5 Disorders with Limited Therapeutic Options in Acute Illness 4.3 Suspicion of an Inborn Error of Metabolism in a Neonate 4.4 Presentation of a Newborn with Intoxication Syndrome 4.4.1 Biochemical Diagnostics 4.5 Treating a Neonate with Intoxication Syndrome 4.5.1 Stage 1 – Provision of Glucose, Cessation of Feedings 4.5.2 Stage 2 – Medical Management 4.5.3 Stage 3 – Detoxification 4.5.4 Stage 4 – Promotion of Anabolism 4.5.5 Stage 5 – Other Supportive Treatment 4.6 Summary References 5: Anabolism: Practical Strategies 5.1 Background 5.2 Importance of Anabolism in Metabolic Diseases 5.3 Fasting and Postprandial Metabolism 5.4 Daily Management 5.5 Acute Episodes and Hospitalization 5.5.1 Home Management 5.5.2 Hospital Management 5.6 Summary References 6: Protein Requirements in Inherited Metabolic Diseases 6.1 Background 6.2 Biological Value and Digestibility of Protein Composition 6.3 Protein Turnover 6.4 Other Factors Influencing Protein Utilization 6.5 Protein Requirements for the General Population 6.6 Protein Requirements in Inherited Metabolic Diseases 6.6.1 Special Considerations in Protein Requirements 6.7 Medical Foods/Protein Supplements in Management of Aminoacidopathies, Organic Acidemias, and Urea Cycle Disorders 6.8 Assessing Protein Sufficiency and Plasma Amino Acids 6.9 Summary References 7: Laboratory Evaluations in Inherited Metabolic Diseases 7.1 Background 7.2 Routine Laboratory Tests 7.2.1 Acidosis 7.2.2 Ammonia 7.2.3 Glucose and Ketones 7.2.4 Lactate 7.3 Metabolic Laboratory Tests 7.3.1 Amino Acid Analysis 7.3.2 Organic Acid Profile 7.3.3 Carnitine Profile 7.3.4 Acylcarnitine Profile 7.3.5 Metabolomics 7.4 Confirmatory Testing References 8: Gene Therapy for Inherited Metabolic Diseases 8.1 Background 8.2 Inborn Errors of Metabolism 8.3 Overview of Gene-Based Therapy 8.4 Routes of Administration for Gene-Based Therapy 8.4.1 Ex Vivo Gene Replacement Therapy 8.4.2 In Vivo Gene Replacement Therapy 8.5 Delivery Vehicles for Gene-Based Therapy 8.5.1 Viral-Mediated Gene-Based Therapy 8.5.2 Nonviral Gene Transfer 8.6 Other Gene-Based Therapies 8.6.1 Oligonucleotide Therapy and Genome Editing 8.6.2 mRNA Therapy 8.7 Approved Gene Therapies 8.8 Clinical Trials in Inborn Errors of Metabolism (Listed in clinicaltrials.gov) 8.9 Limitations, Complications, Challenges, and Future of Gene-Based Therapy References Part II: Aminoacidopathies 9: Phenylketonuria: Phenylalanine Neurotoxicity 9.1 Background 9.2 Biochemistry 9.3 Genetics 9.4 Diagnosis 9.5 Clinical Presentation 9.6 Nutrition Management 9.7 Phenylalanine Neurotoxicity 9.8 White Matter Pathology 9.9 Gray Matter Pathology 9.10 Summary References 10: Nutrition Management of Phenylketonuria 10.1 Background 10.2 Nutrition Management of an Infant with PKU 10.2.1 Overview of Nutrition Management 10.2.2 Initiating Diet for a Newly Diagnosed Neonate 10.2.3 Monitoring Blood Phenylalanine to Adjust the Diet Prescription 10.2.4 Initiating Complementary Feedings 10.2.5 Simplified Diet 10.3 Nutrition Management of PKU Beyond Infancy 10.3.1 Returning to Diet 10.3.2 Acute Management 10.4 Medical Foods for PKU 10.4.1 Glycomacropetide (GMP)-Based Medical Foods 10.5 Metabolic and Nutrition Monitoring 10.6 Large Neutral Amino Acids as an Alternative Diet Treatment for PKU 10.7 Tetrahydrobiopterin Treatment for PKU 10.8 Summary 10.9 Diet Calculation Examples for an Infant with PKU References 11: Medical and Nutrition Management of Phenylketonuria: Pegvaliase 11.1 Background 11.2 Human Clinical Trials 11.3 Efficacy and Safety 11.4 Hypophenylalaninemia 11.5 Immunogenicity 11.6 Practical Use of Pegvaliase in Phenylketonuria 11.7 Nutrition Management of Patients with PKU Treated with Pegvaliase 11.7.1 Nutrition Management During Pegvaliase Initiation and Titration 11.7.2 Nutrition Management During Diet Normalization 11.7.3 Nutrition Management After Diet Normalization References 12: Nutrition Management of Maternal Metabolic Disorders 12.1 Background 12.2 Maternal Phenylketonuria 12.3 Nutrition Management of MPKU 12.3.1 Phenylalanine and Tyrosine 12.3.2 Protein 12.3.3 Energy 12.3.4 Fat and Essential Fatty Acids 12.3.5 Vitamins and Minerals 12.4 Nutrition Management in Lactation and the Postpartum Period 12.5 Medical Management in Maternal PKU 12.5.1 Sapropterin Dihydrocloride 12.5.2 Pegvaliase 12.6 Monitoring 12.7 Pregnancy in Maple Syrup Urine Disease 12.8 Pregnancy in Propionic Acidemia 12.9 Pregnancy in Methylmalonic Acidemia 12.10 Pregnancy in Urea Cycle Disorders 12.11 Overview of Recommendations for the Nutrition Management for Pregnancies in Women with Disorders of Protein Metabolism 12.11.1 Maintain Normal Maternal Weight Gain During Pregnancy 12.11.2 Maintain Adequate Energy and Protein Nutriture Throughout Pregnancy 12.11.3 Maintain Plasma Amino acid Concentrations Within the Reference Range and Anticipate a Higher Intact Protein Tolerance as Pregnancy Progresses 12.11.4 Plan Ahead for Intercurrent Illness and Complications Affecting Dietary Intake 12.11.5 Refer to an Obstetric Clinic Specializing in High-Risk Pregnancy 12.11.6 Anticipate Postpartum Catabolism 12.12 Pregnancy in Fatty Acid Oxidation Disorders 12.13 Pregnancy in Disorders of Carbohydrate Metabolism 12.14 Summary 12.15 Case Reports 12.16 Diet Example for a Pregnant Woman with PKU References 13: Hereditary Tyrosinemia 13.1 Background 13.2 Biochemistry 13.3 Diagnosis 13.4 Clinical Presentation and Natural History 13.5 Pharmaceutical Treatment of Tyrosinemia Type 1 13.6 Nutrition Management 13.7 Monitoring 13.8 Summary References 14: Homocystinuria and Cobalamin Disorders 14.1 Homocystinuria Background 14.2 Biochemistry 14.3 Clinical Presentation 14.3.1 Eyes 14.3.2 Skeletal 14.3.3 Central Nervous System 14.3.4 Vascular System 14.3.5 Other 14.4 Natural History 14.5 Diagnosis 14.6 Pathophysiology 14.7 Management 14.8 Monitoring and Outcome 14.9 Cobalamin Disorders: Background 14.10 Clinical Presentation 14.11 Management and Outcome References 15: Nutrition Management of Homocystinuria and Cobalamin Disorders 15.1 Background 15.2 Nutrition Management 15.2.1 Chronic Management of HCU 15.3 Adjunct Treatments for Homocystinuria 15.4 Monitoring 15.4.1 Growth 15.4.2 Laboratory Monitoring 15.5 Acute Nutrition Management 15.6 Pregnancy 15.7 Homocystinuria Summary 15.8 Background Cobalamin Disorders 15.9 Nutrition Management 15.9.1 Chronic Management Cobalamin Disorders 15.10 Adjunct Therapy for Cobalamin 15.11 Monitoring 15.12 Acute Management 15.13 Cobalamin Disorders Summary 15.14 Diet Example Diet Calculation Example for an Infant with Vitamin B6 Nonresponsive Homocystinuria References 16: Nutrition Management of Urea Cycle Disorders 16.1 Background 16.2 Nutrition Management 16.2.1 Chronic Nutrition Management 16.2.2 Acute Nutrition Management 16.2.2.1 Nutrition Management During Hospitalization 16.2.2.2 Nutrition Management During Illness at Home 16.3 Monitoring 16.3.1 Plasma Amino Acids Related to Dietary Intake 16.3.2 Additional Plasma Amino Acids to Evaluate Based on Diagnosis 16.4 Transplantation 16.5 New Treatment Options 16.6 Summary 16.7 Diet Calculation Example References 17: Nutrition Management of Maple Syrup Urine Disease 17.1 Background 17.2 Nutrition Management 17.2.1 Chronic Nutrition Management 17.2.2 Acute Nutrition Management 17.3 Monitoring 17.4 Transplantation 17.5 Summary 17.6 Diet Calculation Example 17.6.1 MSUD Diet Calculation Example Using Standard Infant Formula as the Source of Leucine and Intact Protein References Part III: Organic Acidemias 18: Organic Acidemias 18.1 Background 18.2 Clinical Presentation 18.2.1 Severe Neonatal Onset Form 18.2.2 Chronic Late Onset Form 18.2.3 Laboratory Studies and Diagnosis 18.2.4 Complications 18.3 Pathophysiology 18.4 Management 18.5 Monitoring 18.6 Summary References 19: Glutaric Acidemia Type I: Diagnosis and Management 19.1 Background 19.2 Clinical, Genetic, and Biochemical Findings 19.3 Diagnosis and Management 19.4 Treatment 19.5 Summary References 20: Nutrition Management of Glutaric Acidemia Type 1 20.1 Background 20.2 Nutrition Management 20.2.1 Chronic Nutrition Management 20.2.2 Acute Nutrition Management 20.3 Monitoring 20.4 Diet After the Age of 6 20.5 Summary 20.6 Diet Calculation Example References 21: Nutrition Management of Propionic Acidemia and Methylmalonic Acidemia 21.1 Background 21.2 Nutrition Management 21.2.1 Initial Nutrition Management of the Acutely Ill Newborn 21.2.2 Chronic Nutrition Management 21.3 Adjunct Treatments for Propionic Acidemia and Methylmalonic Acidemia 21.4 Monitoring 21.4.1 Nutritional Evaluation 21.4.2 Anthropometrics 21.4.3 Laboratory Monitoring 21.5 Acute Nutrition Management During Illness 21.6 Long-Term Complications 21.7 Transplantation 21.8 Summary 21.9 Diet Case Examples References Part IV: Fatty Acid Oxidation Disorders 22: Fatty Acid Oxidation Disorders 22.1 Background 22.2 Biochemistry 22.2.1 Carnitine Cycle 22.2.2 Fatty Acid Beta-Oxidation 22.2.3 Ketogenesis and Ketone Utilization 22.3 Phenotypic Overview of Fatty Acid Oxidation Disorders 22.4 Diagnostic Testing 22.5 Overview of Selected Fatty Acid Oxidation Disorders 22.5.1 Medium Chain Acyl-Coenzyme A Dehydrogenase (MCAD) Deficiency 22.5.2 Long Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase (LCHAD) Deficiency 22.5.3 Very Long Chain Acyl-Coenzyme A Dehydrogenase (VLCAD) Deficiency 22.6 Overview of Ketogenesis and Ketolysis Defects 22.6.1 Ketogenesis 22.6.2 Ketolysis Defects 22.7 Summary References 23: Nutrition Management of Fatty Acid Oxidation Disorders 23.1 Background 23.2 Management of Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) 23.2.1 Chronic Nutrition Management 23.2.2 Treating Illness 23.2.3 Fasting 23.2.4 Diet Modifications 23.2.5 Diet After Infancy 23.2.6 Supplements 23.2.7 Diet for Exercise 23.3 Monitoring of Patients with LC-FAOD 23.4 Nutrition Management of Medium-Chain Acyl Co-A Dehydrogenase Deficiency (MCAD) 23.4.1 Chronic Management 23.5 Acute Nutrition Management in FAOD (MCAD and LC-FAOD) 23.6 Summary 23.7 Diet Calculations Examples References Part V: Disorders of Carbohydrate Metabolism 24: Nutrition Management of Galactosemia 24.1 Background 24.2 Nutrition Management 24.3 Monitoring 24.4 Summary References 25: Glycogen Storage Diseases 25.1 Background 25.2 Glycogen Storage Diseases 25.2.1 Glycogen Storage Diseases Primarily Involving the Liver 25.2.1.1 Glycogen Storage Disease Type I 25.2.1.2 Glycogen Storage Diseases Type VI 25.2.2 Glycogen Storage Diseases Involving Both Liver and Muscle 25.2.2.1 Glycogen Storage Disease Type III: Debranching Enzyme Deficiency 25.2.2.2 Glycogen Storage Diseases Type IX 25.2.2.3 Glycogen Storage Disease Type IV: Branching Enzyme Deficiency 25.2.3 Selected Glycogen Storage Disease Primarily Involving the Muscle 25.2.3.1 Glycogen Storage Diseases Type II (Pompe Disease, Acid α-1,4 Glucosidase Deficiency) 25.2.3.2 Glycogen Storage Disease Type V (Muscle Phosphorylase Deficiency, McArdle Disease) 25.3 Summary References 26: Nutrition Management of Glycogen Storage Disease 26.1 GSD Background 26.2 GSD Type I Background 26.3 Nutrition Management GSD Type I 26.3.1 Diet Principles for Infants 26.3.2 Nutrition Assessment and Diet Composition 26.3.3 Fasting and Overnight Feedings 26.3.4 Supplements for GSD Type I 26.3.5 Cornstarch Therapy for GSD Type I 26.3.6 Glycosade® Therapy for GSD Type I 26.4 Nutrition Management in Special Circumstances 26.4.1 Exercise 26.4.2 Treating Hypoglycemia and Illness 26.4.3 Monitoring 26.5 GSD Type III Background 26.6 Nutrition Management GSD Type III 26.6.1 Cornstarch Therapy for GSD Type III 26.6.2 Glycosade® Therapy for GSD Type III 26.6.3 Supplements for GSD Type III 26.6.4 Adjunct Therapy 26.7 Blood Glucose Monitoring 26.8 Summary 26.9 Diet Calculation Example References Appendix A. Nutrient Composition of Frequently Used Parenteral Fluids Carbohydrate Protein Fat Appendix B. Maintenance Fluid Requirements Appendix C. Energy Needs Required for Anabolism During Acute Illness Appendix D. Dietary Reference Intakes Appendix E. Carnitine in Inherited Metabolic Diseases Carnitine The Carnitine Shuttle L-Carnitine Food Sources and Supplementation Appendix F. Quick Guide to Acylcarnitine Profiles Appendix G. Simplified Diet Appendix H. Interpreting Quantitative Fatty Acid Profiles Plasma Fatty Acids Appendix I. Calculation of Glucose Infusion Rate and Cornstarch Dosing for Patients with Glycogen Storage Disease Example GIR Calculations Example 1 Example 2 Current Dose New Dose Appendix J. Guide to Counting Carbohydrates for Patients with GSD Type 1 Appendix K: At-A-Glance K-1 Glutaric Aciduria K-2 Homocystinuria K-3 Maple Syrup Urine Disease K-4 Methylmalonic acidemia/ Propionic acidemia K-5 Phenylketonuria K-6 Tyrosinemia K-7 Urea Cycle Disorder K-8 Very Long-Chain Acyl-CoA Dehydrogenase Deficiency Index