Inborn Metabolic Diseases - Diagnosis and Treatment
von: Jean-Marie Saudubray, Matthias R. Baumgartner, John Walter
Springer-Verlag, 2016
ISBN: 9783662497715
Sprache: Englisch
655 Seiten, Download: 7802 KB
Format: PDF, auch als Online-Lesen
geeignet für:
| Preface to the 6th edition | 5 | ||
| Content | 6 | ||
| List of Contributors | 26 | ||
| Section I Diagnosis and Treatment: General Principles | 32 | ||
| 1Clinical Approach to Inborn Errors of Metabolism in Pediatrics | 33 | ||
| Classification | 34 | ||
| Pathophysiology | 34 | ||
| Clinical Presentation | 35 | ||
| Antenatal Symptoms | 36 | ||
| Neonatal and Early Infancy Presentation (<1 year) | 38 | ||
| Clinical Presentation | 38 | ||
| Metabolic Derangements and Diagnostic Tests | 44 | ||
| Later Onset Acute and Recurrent Attacks (Late Infancy and Beyond) | 48 | ||
| Clinical Presentations | 48 | ||
| Metabolic Derangements and Diagnostic Tests | 56 | ||
| Chronic and Progressive Neurological Symptoms (Mental Retardation , Developmental Delay , Epilepsy , Neurological Deterioration | 62 | ||
| Diagnostic Approach to Neurological and Mental Deterioration Related to Age | 62 | ||
| Specific Neurosensorial, Neuro-physiological and Neuroradiological Signs and Symptoms (at any Age) | 75 | ||
| Recommended Laboratory Tests in Neurological Syndromes | 82 | ||
| Specific Organ Signs and Symptoms | 85 | ||
| Cardiology | 85 | ||
| Dermatology | 85 | ||
| Endocrinology (. Table 1.34) | 87 | ||
| Gastroenterology and Nutritional Findings | 88 | ||
| Haematology | 91 | ||
| Hepatology | 93 | ||
| Immunology (see also | 94 | ||
| Section 1.6 Neutropenia) | 94 | ||
| Myology | 95 | ||
| Nephrology (. Table 1.39) | 95 | ||
| Neurology and Psychiatry | 95 | ||
| Ophthalmologic Signs | 95 | ||
| Orthopedy (. Table 1.42) | 96 | ||
| Pneumology | 98 | ||
| Psychiatry | 98 | ||
| Rheumatology | 98 | ||
| Stomatology | 99 | ||
| References | 99 | ||
| 2Inborn Errors of Metabolism in Adults : A Diagnostic Approach to Neurological and Psychiatric Presentations | 101 | ||
| Differences Between Paediatric and Adult Phenotypes | 102 | ||
| General Approach to IEM in Adulthood | 102 | ||
| Disorders of Energy Metabolism | 102 | ||
| Disorders of Lipid Metabolism | 102 | ||
| Intoxication Syndromes | 105 | ||
| Disorders of Neurotransmitter Metabolism | 106 | ||
| Metal Storage Disorders | 106 | ||
| Specific Approaches to Neuro-metabolic Presentations in Adults | 106 | ||
| Encephalopathies /Coma s | 106 | ||
| Strokes and Pseudostrokes | 107 | ||
| Movement Disorders | 107 | ||
| Peripheral Neuropathies | 107 | ||
| Leukoencephalopathies | 109 | ||
| Epilepsy | 111 | ||
| Psychiatric Disorders | 112 | ||
| Spastic Paraparesis | 114 | ||
| Cerebellar Ataxia | 114 | ||
| Myopathy | 115 | ||
| Others | 117 | ||
| References | 119 | ||
| 3Diagnostic Procedures | 120 | ||
| Introduction | 121 | ||
| Basal Metabolic Investigation | 121 | ||
| Amino and organic acids | 121 | ||
| Metabolic Profile over the Course of the Day | 121 | ||
| Metabolomic Approaches :the Example of In Vitro 1H-NMRSpectroscopy of Body Fluids | 129 | ||
| Functional Tests | 130 | ||
| Fasting Test | 130 | ||
| Oral Glucose Loading Test | 132 | ||
| Glucagon Test | 132 | ||
| Protein and Allopurinol Loading Test | 132 | ||
| Exercise Test | 133 | ||
| Next Generation Sequencing and Gene panels | 133 | ||
| Postmortem Protocol | 134 | ||
| Cells and Tissues for Enzyme Assays | 134 | ||
| Cells and Tissues for Chromosome and DNA Investigations | 134 | ||
| Skin Fibroblasts | 134 | ||
| Body Fluids for Chemical Investigations | 134 | ||
| Autopsy | 135 | ||
| References | 136 | ||
| 4Emergency Treatments | 137 | ||
| Introduction | 138 | ||
| General Principles | 138 | ||
| Supportive Care | 138 | ||
| Nutrition | 138 | ||
| Specific Therapies | 138 | ||
| Extracorporeal Procedures for Toxin Removal | 138 | ||
| Emergency Management of Particular Clinical Presentations | 139 | ||
| Neurological Deterioration | 139 | ||
| Liver Failure | 142 | ||
| Neonatal Hypoglycaemia | 142 | ||
| Cardiac Failure | 143 | ||
| Primary Hyperlactataemia | 143 | ||
| Intractable Seizures | 143 | ||
| Final Considerations | 143 | ||
| References | 143 | ||
| Section II Disorders of Carbohydrate Metabolism | 146 | ||
| 5The Glycogen Storage Diseases and Related Disorders | 147 | ||
| Hepatic Glycogenoses | 149 | ||
| Liver Glycogen Storage Disease Type 0 (GSD 0a) | 149 | ||
| Glycogen Storage Disease Type I(GSD I) | 149 | ||
| Glycogen Storage Disease Type III (GSD III) | 153 | ||
| Glycogen Storage Disease Type IV (GSD IV) | 154 | ||
| Glycogen Storage Disease Type VI (GSD VI) | 155 | ||
| Glycogen storage disease type IX (GSD IX) | 155 | ||
| Fanconi-Bickel Syndrome | 155 | ||
| Muscle and Cardiac Glycogenoses | 156 | ||
| Glycogen Storage Disease Type V (Myophosphorylase Deficiency , McArdle Disease ) | 156 | ||
| Disorders of Glycolysis | 157 | ||
| Glycogen Storage Disease Type II (Pompe Disease ) | 157 | ||
| Danon Disease (LAMP-2 Deficiency ) | 158 | ||
| Glycogen Depletion Syndromes : Muscle Glycogen Synthase Deficiency (Muscle GSD Type 0, GSD 0b) and Glycogenin 1 Deficiency | 159 | ||
| Muscle and Cardiac Glycogenosis with Polyglucosan Bodies Due to RBCK1 and GYG1 Mutations | 159 | ||
| AMP-activated Protein Kinase (AMPK) Deficiency | 160 | ||
| Brain Glycogenoses | 160 | ||
| Lafora Disease (Neuronal Laforin/ Malin Defects ) | 160 | ||
| Adult Polyglucosan Body Disease | 161 | ||
| References | 161 | ||
| 6Disorders of Galactose Metabolism | 164 | ||
| Galactose-1-Phosphate Uridylyl-transferase (GALT) Deficiency | 166 | ||
| Clinical Presentation of GALT Deficiency | 166 | ||
| Metabolic Derangement in GALT Deficiency | 167 | ||
| Genetics of GALT Deficiency | 167 | ||
| Diagnostic Tests for GALT Deficiency | 167 | ||
| Treatment and Prognosis for GALT Deficiency | 168 | ||
| Uridine Diphosphate Galactose 4’-Epimerase (GALE) Deficiency | 169 | ||
| Clinical Presentation of GALE Deficiency | 169 | ||
| Metabolic Derangement in GALE Deficiency | 169 | ||
| Genetics of GALE Deficiency | 170 | ||
| Diagnostic Tests for GALE Deficiency | 170 | ||
| Treatment and Prognosis for GALE Deficiency | 170 | ||
| Galactokinase (GALK) Deficiency | 170 | ||
| Clinical Presentation of GALK Deficiency | 170 | ||
| Metabolic Derangement in GALK Deficiency | 170 | ||
| Genetics of GALK Deficiency | 170 | ||
| Diagnostic Tests for GALK Deficiency | 171 | ||
| Treatment and Prognosis for GALK Deficiency | 171 | ||
| Fanconi-Bickel Syndrome | 171 | ||
| Portosystemic Venous Shunting and Hepatic Arteriovenous Malformations | 171 | ||
| References | 171 | ||
| 7Disorders of Glycolysis and the Pentose Phosphate Pathway | 173 | ||
| Muscle Phosphofructokinase (PFKM) Deficiency | 175 | ||
| Clinical Presentation | 175 | ||
| Metabolic Derangement | 175 | ||
| Genetics | 175 | ||
| Diagnostic Tests | 176 | ||
| Aldolase A (ALDOA) Deficiency | 176 | ||
| Clinical Presentation | 176 | ||
| Metabolic Derangement | 176 | ||
| Genetics | 176 | ||
| Diagnostic Tests | 176 | ||
| Treatment and Prognosis | 176 | ||
| Triosephosphate Isomerase (TPI) Deficiency | 176 | ||
| Clinical Presentation | 176 | ||
| Metabolic Derangement | 176 | ||
| Genetics | 177 | ||
| Diagnostic Tests | 177 | ||
| Treatment and Prognosis | 177 | ||
| Phosphoglycerate Kinase (PGK) Deficiency | 177 | ||
| Clinical Presentation | 177 | ||
| Metabolic Derangement | 177 | ||
| Genetics | 177 | ||
| Diagnostic Tests | 177 | ||
| Treatment and Prognosis | 177 | ||
| Phosphoglycerate Mutase (PGAM) Deficiency | 178 | ||
| Clinical Presentation | 178 | ||
| Metabolic Derangement | 178 | ||
| Genetics | 178 | ||
| Diagnostic Tests | 178 | ||
| Treatment and Prognosis | 178 | ||
| Enolase Deficiency | 178 | ||
| Clinical Presentation | 178 | ||
| Metabolic Derangement | 178 | ||
| Genetics | 178 | ||
| Diagnostic Tests | 178 | ||
| Treatment and Prognosis | 179 | ||
| Lactate Dehydrogenase (LDH) Deficiency | 179 | ||
| Clinical Presentation | 179 | ||
| Metabolic Derangement | 179 | ||
| Genetics | 179 | ||
| Diagnostic Tests | 179 | ||
| Treatment and Prognosis | 179 | ||
| Glycerol Kinase Deficiency (GKD) | 179 | ||
| Clinical Presentation | 179 | ||
| Metabolic Derangement | 179 | ||
| Genetics | 180 | ||
| Diagnostic Tests | 180 | ||
| Treatment and Prognosis | 180 | ||
| Ribose-5-Phosphate Isomerase (RPI) Deficiency | 180 | ||
| Clinical Presentation | 180 | ||
| Metabolic Derangement | 180 | ||
| Genetics | 181 | ||
| Diagnostic Tests | 181 | ||
| Treatment and Prognosis | 181 | ||
| Transaldolase (TALDO) Deficiency | 181 | ||
| Clinical Presentation | 181 | ||
| Metabolic Derangement | 181 | ||
| Genetics | 181 | ||
| Diagnostic Tests | 181 | ||
| Treatment and Prognosis | 182 | ||
| Transketolase (TKT) Deficiency | 182 | ||
| Clinical Presentation | 182 | ||
| Metabolic Derangement | 182 | ||
| Genetics | 182 | ||
| Diagnostic Tests | 182 | ||
| Treatment and Prognosis | 182 | ||
| Sedoheptulokinase (SHPK) Deficiency | 182 | ||
| Clinical Presentation | 182 | ||
| Metabolic Derangement | 183 | ||
| Genetics | 183 | ||
| Diagnostic Tests | 183 | ||
| Treatment and Prognosis | 183 | ||
| References | 183 | ||
| 8Disorders of Fructose Metabolism | 185 | ||
| Essential Fructosuria | 187 | ||
| Clinical Presentation | 187 | ||
| Metabolic Derangement | 187 | ||
| Genetics | 187 | ||
| Diagnosis | 187 | ||
| Treatment and Prognosis | 187 | ||
| Hereditary Fructose Intolerance | 187 | ||
| Clinical Presentation | 187 | ||
| Metabolic Derangement | 188 | ||
| Genetics | 188 | ||
| Diagnosis | 188 | ||
| Differential Diagnosis | 189 | ||
| Treatment and Prognosis | 189 | ||
| Fructose-1,6-Bisphosphatase Deficiency | 189 | ||
| Clinical Presentation | 189 | ||
| Metabolic Derangement | 190 | ||
| Genetics | 190 | ||
| Diagnosis | 190 | ||
| Differential Diagnosis | 191 | ||
| Treatment and Prognosis | 191 | ||
| References | 191 | ||
| 9Congenital Hyperinsulinism | 193 | ||
| Clinical Presentation | 195 | ||
| Metabolic Derangement | 196 | ||
| Genetics | 196 | ||
| Diagnostic Tests | 196 | ||
| Treatment and Prognosis | 197 | ||
| Long-term Medical Management | 198 | ||
| Prognosis | 198 | ||
| References | 198 | ||
| 10Disorders of Glucose Transport | 199 | ||
| Congenital Glucose/Galactose Malabsorption (SGLT1 Deficiency ) | 201 | ||
| Clinical Presentation | 201 | ||
| Metabolic Derangement | 201 | ||
| Genetics | 201 | ||
| Diagnostic Tests | 201 | ||
| Treatment and Prognosis | 202 | ||
| Renal Glucosuria (SGLT2 Deficiency ) | 202 | ||
| Clinical Presentation | 202 | ||
| Metabolic Derangement | 202 | ||
| Genetics | 202 | ||
| Diagnostic Tests | 202 | ||
| Treatment and Prognosis | 202 | ||
| Glucose Transporter-1 Deficiency (GLUT1 Deficiency ) | 202 | ||
| Clinical Presentation | 202 | ||
| Metabolic Derangement | 203 | ||
| Genetics | 203 | ||
| Diagnostic Tests | 203 | ||
| Treatment and Prognosis | 203 | ||
| Fanconi-Bickel Syndrome (GLUT2 Deficiency ) | 204 | ||
| Clinical Presentation | 204 | ||
| Metabolic Derangement | 204 | ||
| Genetics | 204 | ||
| Diagnostic Tests | 204 | ||
| Treatment and Prognosis | 205 | ||
| Arterial Tortuosity Syndrome (GLUT10 Deficiency ) | 205 | ||
| Clinical Presentation | 205 | ||
| Metabolic Derangement | 205 | ||
| Genetics | 205 | ||
| Diagnostic Tests | 205 | ||
| Treatment and Prognosis | 205 | ||
| References | 206 | ||
| Section III Disorders of Mitochondrial Energy Metabolism | 208 | ||
| 11Disorders of Pyruvate Metabolism and the Tricarboxylic Acid Cycle | 209 | ||
| Pyruvate Carboxylase Deficiency | 211 | ||
| Metabolic Derangement | 211 | ||
| Clinical Presentation | 211 | ||
| Genetics | 212 | ||
| Diagnostic Tests | 212 | ||
| Treatment and Prognosis | 212 | ||
| Phosphoenolpyruvate Carboxykinase Deficiency | 214 | ||
| Pyruvate Dehydrogenase Complex Deficiency | 214 | ||
| Clinical Presentation | 214 | ||
| Metabolic Derangement | 215 | ||
| Genetics | 215 | ||
| Diagnostic Tests | 215 | ||
| Treatment and Prognosis | 216 | ||
| Dihydrolipoamide Dehydrogenase Deficiency (DLD) | 216 | ||
| Clinical Presentation | 216 | ||
| Metabolic Derangement | 216 | ||
| Genetics | 216 | ||
| Diagnostic Tests | 216 | ||
| Treatment and Prognosis | 216 | ||
| 2-Ketoglutarate Dehydrogenase Complex Deficiency (KDHC) | 217 | ||
| Clinical Presentation | 217 | ||
| Metabolic Derangement | 217 | ||
| Genetics | 217 | ||
| Diagnostic Tests | 217 | ||
| Treatment and Prognosis | 217 | ||
| Fumarase Deficiency | 217 | ||
| Clinical Presentation | 217 | ||
| Metabolic Derangement | 217 | ||
| Genetics | 218 | ||
| Diagnostic Tests | 218 | ||
| Treatment and Prognosis | 218 | ||
| Succinate Dehydrogenase Deficiency | 218 | ||
| Clinical Presentation | 218 | ||
| Metabolic Derangement | 218 | ||
| Other Krebs Cycle Disorders | 218 | ||
| Pyruvate Transporter Defect | 219 | ||
| Protein-bound lipoic acid defect and defects in cof actors | 219 | ||
| References | 219 | ||
| 12Disorders of Mitochondrial Fatty Acid Oxidation & Riboflavin Metabolism | 222 | ||
| Disorders of Mitochondrial Fatty Acid Oxidation | 224 | ||
| Clinical Presentations | 224 | ||
| Fatty Acid Transport Defects | 224 | ||
| Carnitine Cycle Defects | 224 | ||
| ß-Oxidation Defects | 226 | ||
| Electron Transfer Defects | 227 | ||
| Other Potential Defects | 227 | ||
| Metabolic Derangement | 227 | ||
| Genetics | 228 | ||
| Diagnostic Tests | 228 | ||
| Abnormal Metabolites | 228 | ||
| Studies | 230 | ||
| Fasting Studies | 230 | ||
| Prenatal Diagnosis | 230 | ||
| Newborn Screening | 230 | ||
| Treatment and Prognosis | 230 | ||
| Management of Acute Illness | 230 | ||
| Long Term Dietary Management | 230 | ||
| Drug Treatment | 231 | ||
| Monitoring | 231 | ||
| Prognosis | 232 | ||
| Defects of Riboflavin Transport & Metabolism | 232 | ||
| Brown-Vialetto-van Laere Syndrome | 232 | ||
| RFVT1 Deficiency | 233 | ||
| FAD Synthase and Mitochondrial FAD Transporter Deficiencies | 233 | ||
| References | 233 | ||
| 13Disorders of Ketogenesis and Ketolysis | 235 | ||
| Ketogenesis Defects | 237 | ||
| Clinical Presentation | 237 | ||
| Metabolic Derangement | 237 | ||
| Genetics | 237 | ||
| Diagnostic Tests | 237 | ||
| Treatment and Prognosis | 238 | ||
| Defects of Ketone Body Utilization or Transport | 238 | ||
| Clinical Presentation | 238 | ||
| Metabolic Derangement | 239 | ||
| Genetics | 239 | ||
| Diagnostic Tests | 239 | ||
| Treatment and Prognosis | 239 | ||
| Cytosolic Acetoacetyl-CoA Thiolase Deficiency | 240 | ||
| Ketogenic Diets | 240 | ||
| References | 240 | ||
| 14Disorders of Oxidative Phosphorylation | 242 | ||
| Clinical Presentation | 244 | ||
| Neonatal and Infantile Presentations | 245 | ||
| Presentation in Childhood and Adolescence | 249 | ||
| Adult-Onset Disorders | 250 | ||
| Metabolic Derangement | 250 | ||
| Genetics | 251 | ||
| Mitochondrial DNA Mutations | 251 | ||
| Nuclear Gene Defects | 251 | ||
| Frequency of Mutations | 252 | ||
| Diagnostic Tests | 252 | ||
| Screening Tests | 252 | ||
| Muscle and Other Tissue Biopsies | 254 | ||
| Molecular Genetic Investigations | 257 | ||
| Treatment and Prognosis | 257 | ||
| Treatable Disorders | 257 | ||
| Supportive Management | 259 | ||
| Vitamin and Cofactor Cocktails | 259 | ||
| Experimental Approaches | 259 | ||
| Genetic Counselling and Prenatal and Preimplantation Genetic Diagnosis | 259 | ||
| Prognosis | 259 | ||
| References | 260 | ||
| 15Creatine Deficiency Syndromes | 262 | ||
| Clinical Presentation | 264 | ||
| Arginine Glycine Amidinotransferase (AGAT) Deficiency | 264 | ||
| Guanidinoacetate Methyltransferase (GAMT) Deficiency | 264 | ||
| Creatine Transporter (CRTR) Deficiency | 264 | ||
| Metabolic Derangement | 264 | ||
| Genetics | 265 | ||
| Diagnostic Tests | 265 | ||
| Brain MRS | 265 | ||
| Metabolite Analysis | 265 | ||
| DNA Analysis | 265 | ||
| Functional Tests | 266 | ||
| Prenatal Diagnosis | 266 | ||
| Newborn Screening | 266 | ||
| Treatment and Prognosis | 266 | ||
| Deficiency | 266 | ||
| GAMT Deficiency | 266 | ||
| CRTR Deficiency | 266 | ||
| References | 266 | ||
| Section IV Disorders of Amino Acid Metabolism and Transport | 268 | ||
| 16Hyperphenylalaninaemia | 270 | ||
| Phenylalanine Hydroxylase Deficiency | 272 | ||
| Clinical Presentation | 272 | ||
| Metabolic Derangement | 272 | ||
| Genetics | 272 | ||
| Diagnostic Tests | 272 | ||
| Treatment and Prognosis | 273 | ||
| Maternal PKU | 277 | ||
| Clinical Presentation | 277 | ||
| Metabolic Derangement | 277 | ||
| Treatment and Prognosis | 277 | ||
| HPA and Disorders of Biopterin Metabolism | 278 | ||
| Clinical Presentation | 278 | ||
| Metabolic Derangement | 278 | ||
| Genetics | 278 | ||
| Diagnostic and Confirmatory Tests | 278 | ||
| Treatment and Prognosis | 279 | ||
| References | 280 | ||
| 17Disorders of Tyrosine Metabolism | 283 | ||
| Hereditary Tyrosinaemia Type I (Hepatorenal Tyrosinaemia ) | 285 | ||
| Clinical Presentation | 285 | ||
| Metabolic Derangement | 285 | ||
| Genetics | 286 | ||
| Diagnostic Tests | 286 | ||
| Treatment and Prognosis | 287 | ||
| Hereditary Tyrosinaemia Type II (Oculocutaneous Tyrosinaemia , Richner-Hanhart Syndrome ) | 288 | ||
| Clinical Presentation | 288 | ||
| Metabolic Derangement | 288 | ||
| Genetics | 289 | ||
| Diagnostic Tests | 289 | ||
| Treatment and Prognosis | 289 | ||
| Hereditary Tyrosinaemia Type III | 289 | ||
| Clinical Presentation | 289 | ||
| Metabolic Derangement | 289 | ||
| Genetics | 289 | ||
| Diagnostic Tests | 290 | ||
| Treatment and Prognosis | 290 | ||
| Transient Tyrosinaemia | 290 | ||
| Alkaptonuria | 290 | ||
| Clinical Presentation | 290 | ||
| Metabolic Derangement | 290 | ||
| Genetics | 291 | ||
| Diagnostic Tests | 291 | ||
| Treatment and Prognosis | 291 | ||
| Hawkinsinuria | 291 | ||
| Clinical Presentation | 291 | ||
| Metabolic Derangement | 291 | ||
| Genetics | 291 | ||
| Diagnostic Tests | 291 | ||
| Treatment and Prognosis | 292 | ||
| References | 292 | ||
| 18Branched-chain Organic Acidurias /Acidaemias | 294 | ||
| Maple Syrup Urine Disease , Isovaleric Aciduria , Propionic Aciduria , Methylmalonic Aciduria | 296 | ||
| Clinical Presentation | 296 | ||
| Metabolic Derangement | 298 | ||
| Genetics | 299 | ||
| Diagnostic Tests | 300 | ||
| Treatment and Prognosis | 300 | ||
| 3-Methylcrotonyl Glycinuria | 305 | ||
| Clinical Presentation | 305 | ||
| Metabolic Derangement | 305 | ||
| Genetics | 305 | ||
| Diagnostic Tests | 306 | ||
| Treatment and Prognosis | 306 | ||
| 3-Methylglutaconic Aciduria | 306 | ||
| Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency | 307 | ||
| 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency | 307 | ||
| Isobutyryl-CoA Dehydrogenase Deficiency | 307 | ||
| 3-Hydroxyisobutyric Aciduria | 307 | ||
| Malonyl-CoA Decarboxylase Deficiency | 308 | ||
| ACSF3 Deficiency | 308 | ||
| Enoyl-CoA Hydratase or ECHS1 Deficiency | 308 | ||
| References | 308 | ||
| 19Disorders of the Urea Cycle and Related Enzymes | 312 | ||
| Mitochondrial Urea Cycle Disorders | 314 | ||
| Clinical Presentation | 314 | ||
| Genetics | 315 | ||
| Diagnostic Tests | 315 | ||
| Metabolic Derangements | 315 | ||
| Treatment and Prognosis | 317 | ||
| Cytosolic Urea Cycle Disorders | 318 | ||
| Clinical Presentation | 318 | ||
| Metabolic Derangements | 319 | ||
| Genetics | 319 | ||
| Diagnostic Tests | 319 | ||
| Treatment and Prognosis | 320 | ||
| Urea Cycle Mitochondrial Transporter Defects | 320 | ||
| Hyperornithinemia , Hyperammonaemia and Homocitrullinuria (HHH) Syndrome | 320 | ||
| Citrin Deficiency | 320 | ||
| Urea Cycle Defects due to Deficiencies of Ancillary Enzymes | 322 | ||
| .1-Pyrroline-5-Carboxylate Synthetase (P5CS) Deficiency | 322 | ||
| Carbonic Anhydrase Va (CAVA) Deficiency | 322 | ||
| References | 323 | ||
| 20Disorders of Sulfur Amino Acid Metabolism | 326 | ||
| Methionine S-Adenosyltransferase Deficiency (Mudd’s Disease ) | 328 | ||
| Clinical Presentation | 328 | ||
| Metabolic Derangement | 328 | ||
| Genetics | 328 | ||
| Diagnostic Tests | 328 | ||
| Treatment and Prognosis | 330 | ||
| Glycine N-Methyltransferase Deficiency | 330 | ||
| Clinical Presentation | 330 | ||
| Metabolic Derangement | 330 | ||
| Genetics | 330 | ||
| Diagnostic Tests | 330 | ||
| Treatment and Prognosis | 330 | ||
| S-Adenosylhomocysteine Hydrolase Deficiency | 330 | ||
| Clinical Presentation | 330 | ||
| Metabolic Derangement | 330 | ||
| Genetics | 330 | ||
| Diagnostic Tests | 330 | ||
| Treatment and Prognosis | 331 | ||
| Adenosine Kinase Deficiency | 331 | ||
| Cystathionine ß-Synthase Deficiency | 331 | ||
| Clinical Presentation | 331 | ||
| Metabolic Derangement | 331 | ||
| Genetics | 331 | ||
| Diagnostic Tests | 332 | ||
| Treatment and Prognosis | 333 | ||
| Cystathionine .-Lyase Deficiency | 334 | ||
| Clinical Presentation | 334 | ||
| Metabolic Derangement | 334 | ||
| Genetics | 334 | ||
| Diagnostic Tests | 334 | ||
| Treatment and Prognosis | 334 | ||
| Molybdenum Cofactor Deficiency | 334 | ||
| Clinical Presentation | 334 | ||
| Metabolic Derangement | 334 | ||
| Genetics | 334 | ||
| Diagnostic Tests | 334 | ||
| Treatment and Prognosis | 334 | ||
| Isolated Sulfite Oxidase Deficiency | 335 | ||
| Clinical Presentation | 335 | ||
| Metabolic Derangement | 335 | ||
| Genetics | 335 | ||
| Diagnostic Tests | 335 | ||
| Treatment and Prognosis | 335 | ||
| Ethylmalonic Encephalopathy | 335 | ||
| Clinical Presentation | 335 | ||
| Metabolic Derangement | 335 | ||
| Genetics | 335 | ||
| Diagnostic Tests | 335 | ||
| Treatment and Prognosis | 335 | ||
| References | 336 | ||
| 21Disorders of Ornithine and Proline Metabolism | 338 | ||
| Hyperornithinaemia Due to Ornithine Aminotransferase Deficiency (Gyrate Atrophy of the Choroid and Retina ) | 340 | ||
| Hyperornithinaemia , Hyperammonaemia and Homocitrullinuria (HHH) Syndrome | 342 | ||
| .1-Pyrroline-5-Carboxylate Synthetase Deficiency | 344 | ||
| .1-Pyrroline-5-Carboxylate Reductase Deficiency 1 (PYCR1) and 2 (PYCR2) | 345 | ||
| Proline Oxidase Deficiency (Hyperprolinaemia Type I ) | 345 | ||
| .1-Pyrroline-5-Carboxylate Dehydrogenase Deficiency (Hyperprolinaemia Type II) | 346 | ||
| Prolidase Deficiency | 346 | ||
| Spermine Synthase Deficiency (Snyder Robinson Syndrome ) | 347 | ||
| References | 347 | ||
| 22Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism | 349 | ||
| Introduction | 351 | ||
| Hyperlysinaemia /Saccharopinuria | 353 | ||
| Clinical Presentation | 353 | ||
| Metabolic Derangement | 353 | ||
| Genetics | 354 | ||
| Diagnostic Tests | 354 | ||
| Treatment and Prognosis | 354 | ||
| Hydroxylysinuria | 354 | ||
| 2-Amino -/2-Oxoadipic Aciduria | 354 | ||
| Clinical Presentation | 354 | ||
| Metabolic Derangement | 354 | ||
| Genetics | 355 | ||
| Diagnostic Tests | 355 | ||
| Treatment and Prognosis | 355 | ||
| Glutaric Aciduria Type I | 355 | ||
| Clinical Presentation | 355 | ||
| Metabolic Derangement | 356 | ||
| Genetics | 356 | ||
| Diagnostic Tests | 356 | ||
| Treatment and Prognosis | 357 | ||
| Glutaric Aciduria Type III | 358 | ||
| Clinical Presentation | 358 | ||
| Metabolic Derangement | 358 | ||
| Genetics | 358 | ||
| Diagnostic Tests | 358 | ||
| Treatment and Prognosis | 358 | ||
| L-2-Hydroxyglutaric Aciduria | 358 | ||
| Clinical Presentation | 358 | ||
| Metabolic Derangement | 359 | ||
| Genetics | 359 | ||
| Diagnostic Tests | 359 | ||
| Treatment and Prognosis | 359 | ||
| D-2-Hydroxyglutaric Aciduria | 359 | ||
| Clinical Presentation | 359 | ||
| Metabolic Derangement | 359 | ||
| Genetics | 360 | ||
| Diagnostic Tests | 360 | ||
| Treatment and Prognosis | 360 | ||
| D-2-/L-2-Hydroxyglutaric Aciduria | 360 | ||
| Clinical Presentation | 360 | ||
| Metabolic Derangement | 360 | ||
| Genetics | 360 | ||
| Diagnostic Tests | 360 | ||
| Treatment and Prognosis | 360 | ||
| N-Acetylaspartic Aciduria (Canavan Disease ) | 360 | ||
| Clinical Presentation | 360 | ||
| Metabolic Derangement | 361 | ||
| Genetics | 361 | ||
| Diagnostic Tests | 361 | ||
| Treatment and Prognosis | 361 | ||
| Aminoacylase 1 Deficiency | 361 | ||
| Diagnostic Tests | 362 | ||
| Treatment and Prognosis | 362 | ||
| Hypoacetylaspartia and AspartateGlutamate Carrier 1 Deficiency | 362 | ||
| References | 362 | ||
| 23Nonketotic Hyperglycinemia (Glycine Encephalopathy ) and Lipoate Deficiency Disorders | 365 | ||
| Introduction: Definitions | 366 | ||
| Clinical Presentation | 367 | ||
| Severe Classic NKH | 367 | ||
| Attenuated Classic NKH | 367 | ||
| Lipoate Disorders Including Variant NKH | 368 | ||
| Metabolic Derangement | 368 | ||
| Genetics | 369 | ||
| Diagnostic Tests | 369 | ||
| Treatment | 370 | ||
| Prognosis | 371 | ||
| References | 371 | ||
| 24Disorders of Glutamine , Serine and Asparagine Metabolism | 373 | ||
| Glutamine Synthetase Deficiency | 375 | ||
| Inborn Errors of Serine Meta bolism | 375 | ||
| 3-Phosphoglycerate Dehydrogenase Deficiency | 375 | ||
| Phosphoserine Aminotransferase Deficiency | 376 | ||
| 3-Phosphoserine Phosphatase Deficiency | 376 | ||
| Brain Serine Transporter Deficiency | 376 | ||
| Serine Palmitoyltransferase Defects | 377 | ||
| Asparagine Synthetase Deficiency | 377 | ||
| References | 377 | ||
| 25Disorders of Amino Acid Transport at the Cell Membrane | 379 | ||
| Cystinuria | 381 | ||
| Clinical Presentation | 381 | ||
| Metabolic Derangement | 381 | ||
| Genetics | 381 | ||
| Diagnostic Tests | 381 | ||
| Treatment and Prognosis | 382 | ||
| Lysinuric Protein Intolerance | 383 | ||
| Clinical Presentation | 383 | ||
| Metabolic Derangement | 383 | ||
| Genetics | 384 | ||
| Diagnostic Tests | 384 | ||
| Treatment and Prognosis | 384 | ||
| Hartnup Disease | 385 | ||
| Clinical Presentation | 385 | ||
| Metabolic Derangement | 385 | ||
| Genetics | 385 | ||
| Diagnostic Tests | 385 | ||
| Treatment and Prognosis | 386 | ||
| Asymptomatic Aminoacidurias: Iminoglycinuria and Dicarboxylic Aminoaciduria | 386 | ||
| References | 386 | ||
| Section V Vitamin-Responsive Disorders | 388 | ||
| 26Biotin-responsive Disorders | 389 | ||
| Clinical Presentation | 391 | ||
| Holocarboxylase Synthetase Deficiency | 392 | ||
| Biotinidase Deficiency | 392 | ||
| Metabolic Derangement | 392 | ||
| Genetics | 393 | ||
| Holocarboxylase Synthetase Deficiency | 393 | ||
| Biotinidase Deficiency | 393 | ||
| Diagnostic Tests | 393 | ||
| Holocarboxylase Synthetase Deficiency | 394 | ||
| Biotinidase Deficiency | 394 | ||
| Acquired Biotin Deficiency | 394 | ||
| Prenatal Diagnosis | 394 | ||
| Treatment and Prognosis | 394 | ||
| Holocarboxylase Synthetase Deficiency | 395 | ||
| Biotinidase Deficiency | 395 | ||
| References | 396 | ||
| 27Disorders of Cobalamin and Folate Transport and Metabolism | 398 | ||
| Disorders of Absorption and Transport of Cobalamin | 400 | ||
| Hereditary Intrinsic Factor Deficiency | 400 | ||
| Defective Transport of Cobalamin by Enterocytes (Imerslund-Gräsbeck Syndrome ) | 400 | ||
| Haptocorrin (R Binder) Deficiency | 401 | ||
| Transcobalamin Deficiency | 401 | ||
| Transcobalamin Receptor Deficiency | 402 | ||
| Disorders of Intracellular Utilisation of Cobalamin | 402 | ||
| Combined Deficiencies of Adenosylcobalamin and Methylcobalamin | 402 | ||
| Adenosylcobalamin Deficiency | 405 | ||
| Methylcobalamin Deficiency | 405 | ||
| Disorders of Absorption and Metabolism of Folate | 407 | ||
| Hereditary Folate Malabsorption | 407 | ||
| Cerebral Folate Deficiency | 407 | ||
| Methylenetetrahydrofolate Dehydrogenase (MTHFD1) Deficiency | 408 | ||
| Dihydrofolate Reductase Deficiency | 408 | ||
| Glutamate Formiminotransferase Deficiency | 409 | ||
| Methylenetetrahydrofolate Reductase Deficiency | 409 | ||
| References | 410 | ||
| 28Disorders of Thiamine and Pyridoxine Metabolism | 413 | ||
| Disorders of Thiamine (Vitamin B1) Metabolism | 414 | ||
| Thiamine Transporter 1 (THTR1) Deficiency | 415 | ||
| Thiamine Transporter 2 (THTR2) Deficiency | 416 | ||
| Thiamine Pyrophosphokinase Deficiency | 416 | ||
| Mitochondrial TPP Transporter Deficiency | 417 | ||
| Thiamine-Responsive a-Ketoacid Dehydrogenase Deficiencies | 417 | ||
| Thiamine-Responsive Pyruvate Dehydrogenase Deficiency | 417 | ||
| Thiamine-Responsive Maple Syrup Urine Disease | 418 | ||
| Vitamin B6 Metabolism | 419 | ||
| Antiquitin Deficiency | 420 | ||
| Hyperprolinemia Type II | 421 | ||
| Pyridox(am)ine 5’-phosphate Oxidase (PNPO) Deficiency | 422 | ||
| Congenital Hypophosphatasia | 422 | ||
| Hyperphosphatasia-Mental Retardation Syndrome (HPMRS) | 422 | ||
| Other B6 Responsive Disorders | 422 | ||
| References | 423 | ||
| Section VI Neurotransmitter and Small Peptide Disorders | 425 | ||
| 29Disorders of Neurotransmission | 426 | ||
| Inborn Errors of Gamma Amino Butyric Acid Metabolism | 428 | ||
| Gamma Amino Butyric Acid Transaminase Deficiency | 428 | ||
| Succinic Semialdehyde Dehydrogenase Deficiency | 429 | ||
| Homocarnosinosis | 429 | ||
| Inborn Errors of Receptors and Trans-porters of Neurotransmitters | 430 | ||
| Hyperekplexia | 430 | ||
| GABA Receptor Mutations | 431 | ||
| Glutamate Receptor Mutations | 431 | ||
| Mitochondrial Glutamate Transporter Defect | 431 | ||
| Dopamine Transporter Defect | 432 | ||
| Brain Dopamine-Serotonin Vesicular Transport Defect | 432 | ||
| Inborn Errors of Monoamine Metabolism | 432 | ||
| Tyrosine Hydroxylase Deficiency | 432 | ||
| Aromatic L-Aminoacid Decarboxylase Deficiency | 433 | ||
| Dopamine ß-Hydroxylase Deficiency | 434 | ||
| Monoamine Oxidase-A Deficiency | 434 | ||
| Guanosine Triphosphate Cyclohydrolase-I Deficiency | 435 | ||
| Sepiapterine Reductase Deficiency | 436 | ||
| References | 436 | ||
| 30Trimethylaminuria, Dimethyl-glycine Dehydrogenase Deficiency and Disorders in the Metabolism of Glutathione | 439 | ||
| Trimethylaminuria (Fish Malodour Syndrome ) | 441 | ||
| Metabolic Derangement | 441 | ||
| Genetics | 441 | ||
| Clinical Presentation | 441 | ||
| Diagnostic Tests | 442 | ||
| Treatment | 442 | ||
| Dimethylglycine Dehydrogenase Deficiency | 442 | ||
| Clinical Presentation | 442 | ||
| Metabolic Derangement | 442 | ||
| Genetics | 442 | ||
| Diagnostic Tests | 442 | ||
| Treatment | 443 | ||
| Disorders in the Metabolism of Glutathione | 443 | ||
| y-Glutamylcysteine Synthetase Deficiency | 443 | ||
| Glutathione Synthetase Deficiency | 444 | ||
| y-Glutamyl Transpeptidase Deficiency | 445 | ||
| 5-Oxoprolinase Deficiency | 446 | ||
| Dipeptidase Deficiency | 446 | ||
| Secondary 5-Oxoprolinuria | 446 | ||
| References | 446 | ||
| Section VII Disorders of Lipid and Bile Acid Metabolism | 448 | ||
| 31Inborn Errors of Lipoprotein Metabolism Presenting in Childhood | 449 | ||
| Disorders of Low Density Lipoprotein Metabolism | 451 | ||
| Disorders of Triglyceride (TG) Metabolism | 453 | ||
| Disorders of High Density Lipoprotein Metabolism | 461 | ||
| Disorders of Sterol Storage | 461 | ||
| Conclusion | 461 | ||
| References | 461 | ||
| 32Disorders of Isoprenoid/ Cholesterol Synthesis | 463 | ||
| Mevalonate Kinase Deficiency | 465 | ||
| Smith-Lemli-Opitz Syndrome (7-Dehydrocholesterol Reductase Deficiency ) | 466 | ||
| Sterol .8-.7 Isomerase Deficiency | 467 | ||
| X-Linked Dominant Chondrodysplasia Punctata 2 or Conradi-Hünermann Syndrome in Females | 467 | ||
| Hemizygous EBP Deficiency in Males | 468 | ||
| Deficiency of the C4-Demethylase Complex | 468 | ||
| C4-Methyl Sterol Oxidase Deficiency (SMO Deficiency) | 468 | ||
| Sterol 4a-Carboxylate 3-Dehydrogenase Deficiency | 468 | ||
| Desmosterol Reductase Deficiency (Desmosterolosis) | 469 | ||
| Sterol .5-Desaturase Deficiency (Lathosterolosis) | 469 | ||
| Sterol .14-Reductase Deficiency (Hydrops – Ectopic Calcification – Moth-eaten (HEM) Skeletal Dysplasia or Greenberg Skeletal Dys | 470 | ||
| References | 471 | ||
| 33Disorders of Bile Acid Synthesis | 473 | ||
| 3ß-Hydroxy-.5-C27-Steroid Dehydrogenase Deficiency | 475 | ||
| .4-3-Oxosteroid 5ß-Reductase Deficiency | 476 | ||
| Cerebrotendinous Xanthomatosis (Sterol 27-Hydroxylase Deficiency ) | 477 | ||
| a-Methylacyl-CoA Racemase Deficiency (see also Chapter 40) | 479 | ||
| Oxysterol 7a-Hydroxylase Deficiency | 479 | ||
| Bile Acid Amidation Defect 1 : Bile Acid CoA : Amino Acid N-Acyl Transferase Deficiency | 480 | ||
| Bile Acid Amidation Defect 2 : Bile Acid CoA Ligase Deficiency | 480 | ||
| Cholesterol 7a-Hydroxylase Deficiency | 481 | ||
| Disorders of Peroxisome Biogenesis, Peroxisomal Import and Peroxisomal ß-Oxidation | 481 | ||
| References | 481 | ||
| 34Disorders of Intracellular Triglyceride and Phospholipid Metabolism | 484 | ||
| Inborn Errors of the Common Pathway of Acylglycerol and Phospholipid Synthesis | 486 | ||
| Glycerol-3-phosphate Dehydrogenase 1 (GPD1) Deficiency : Autosomal Recessive Hepatic Steatosis and Hypertriglyceridemia | 486 | ||
| Glycerol Kinase Deficiency is described in Chapter 7 | 486 | ||
| 1-Acylglycerol-3-Phosphate O-Acyltransferase 2 (AGPAT2) Deficiency : Autosomal Recessive Generalized Congenital Lipodystrophy | 486 | ||
| Phosphatidic Acid Phosphatase (PAP | 486 | ||
| Diacylglycerol Kinase Epsilon (DGKE) Deficiency : Atypical Haemolytic Uremic Syndrome | 487 | ||
| Inborn Errors of Cytoplasmic Triglyceride Metabolism | 487 | ||
| Diacylglycerol O-Acyl Transferase 1 (DGAT1) Deficiency : Congenital Diarrhea | 487 | ||
| Perilipin 1 Deficiency : Autosomal Dominant Partial Lipodystrophy | 488 | ||
| Neutral Lipid Storage Diseases (NLSDs) : ATGL and CGI-58 Deficiencies | 488 | ||
| Hormone-Sensitive Lipase (HSL) Deficiency | 488 | ||
| Inborn Errors of Phospholipid Biosynthesis | 490 | ||
| Choline Kinase ß (CHKß) Deficiency: Congenital Muscular Dystrophy, Megaconial Type | 490 | ||
| Choline-PhosphateCytidylyltrans-ferase a (CCTa) Deficiency : Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy or Congenital | 490 | ||
| PhosphatidylserineSynthase 1 (PSS1) Gain of Function (Lenz-Majewski Hyperostotic Dwarfism ) | 490 | ||
| Acylglycerol Kinase (AGK) Deficiency : Myopathy, Hypertrophic Cardiomyopathy and Congenital Cataract (Sengers Syndrome ) | 491 | ||
| Cardiolipin Remodeling Enzyme Deficiency : X-linked Cardiomyopathy and Neutropenia (Barth Syndrome ) | 491 | ||
| Mutation : Methylglutaconic Aciduria, Deafness, Hepatic I nvolvement, Encephalopathy, and Leigh Syndrome (MEGDHEL Syndrome ) | 492 | ||
| Mitochondrial Calcium Independent Phospholipase A2. (iPLA2.): Autosomal Recessive Myopathy, Dystonia and Convulsions (not shown) | 492 | ||
| Inborn Errors related to Phospholipid Remodeling | 492 | ||
| a/ß Hydrolase Domain-Containing Protein 12 (ABHD12) Deficiency : Polyneuropathy, Hearing loss, Ataxia, Retinitis Pigmentosa and | 492 | ||
| Phospholipase A2 Deficiency (PLA2G6) : Autosomal Recessive Infantile Neuroaxonal Dystrophy, Neurodegeneration with Brain Iron Accumulation | 493 | ||
| Deficiencies of Neuropathy TargetEsterase (NTE or PNPLA-6) orMitochondrial Calcium-independentPhospholipase A2? (PNPLA6):Peripheral Neuropathy, SpasticParaplegia, ChorioretinalDegeneration, HypogonadotrophicHypogonadism, Trichomegaly(SPG39, Boucher-Neuhauser , Gordon-Holms , Oliver-McFarlane , Laurence-Moon syndromes ) or MitochondrialMyopathy with Dystonia | 493 | ||
| DDHD1 and DDHD2 Mutations :Hereditary Spastic Paraplegias28 and 45 | 494 | ||
| CYP2U1 Mutation : Spastic Paraplegiawith Basal Ganglia Calcification(Hereditary Spastic Paraplegia 56,SPG56) | 494 | ||
| Inborn Errors of Polyphosphoinositide Metabolism | 495 | ||
| References | 495 | ||
| Section VIII Disorders of Nucleic Acid and Heme Metabolism | 499 | ||
| 35Disorders of Purine and Pyrimidine Metabolism | 500 | ||
| Inborn Errors of Purine Metabolism | 502 | ||
| Phosphoribosyl Pyrophosphate Synthetase Superactivity | 502 | ||
| Phosphoribosyl Pyrophosphate Synthetase Deficiency | 502 | ||
| Adenylosuccinase Deficiency | 503 | ||
| AICA-Ribosiduria | 503 | ||
| Muscle Adenosine Monophosphate Deaminase 1 Deficiency | 503 | ||
| Adenosine Monophosphate Deaminase 2 and 3 Deficiencies | 504 | ||
| Adenosine Deaminase 1 Deficiency | 504 | ||
| Adenosine Deaminase 2 Deficiency | 506 | ||
| Adenosine Deaminase Superactivity | 506 | ||
| Purine Nucleoside Phosphorylase Deficiency | 506 | ||
| Xanthine Oxidase Deficiency | 506 | ||
| Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency | 507 | ||
| Adenine Phosphoribosyl-transferase Deficiency | 508 | ||
| Adenylate Kinase 1 Deficiency | 509 | ||
| Adenylate Kinase 2 Deficiency | 509 | ||
| Adenosine Kinase Deficiency | 509 | ||
| Adenylate Cyclase 5 Mutations | 509 | ||
| IMP Dehydrogenase Mutations | 509 | ||
| Deoxyguanosine Kinase Deficiency | 509 | ||
| Thiopurine Methyltransferase Deficiency | 510 | ||
| Inosine Triphosphatase Deficiency | 510 | ||
| Inborn Errors of Pyrimidine Metabolism | 510 | ||
| CAD (Carbamoylphosphate Synthetase II, Aspartate Transcarba-mylase, Dihydroorotase) Deficiency | 510 | ||
| UMP Synthase Deficiency (Hereditary Orotic Aciduria ) | 510 | ||
| Miller syndrome (Dihydroorotate Dehydrogenase Deficiency ) | 512 | ||
| Dihydropyrimidine Dehydrogenase Deficiency | 512 | ||
| Dihydropyrimidinase Deficiency | 513 | ||
| Ureidopropionase Deficiency | 513 | ||
| Pyrimidine 5’-Nucleotidase Deficiency | 513 | ||
| Cytosolic 5’-Nucleotidase Superactivity | 513 | ||
| Thymidine Phosphorylase Deficiency | 513 | ||
| Cytidine Deaminase Deficiency | 514 | ||
| Thymidine Kinase 2 Deficiency | 514 | ||
| References | 514 | ||
| 36Disorders of Haem Biosynthesis | 519 | ||
| X-Linked Sideroblastic Anaemia | 521 | ||
| The Porphyrias | 521 | ||
| Classification and Diagnosis | 521 | ||
| 5-Aminolevulinic Acid Dehydratase Porphyria | 523 | ||
| Acute Intermittent Porphyria (AIP) | 523 | ||
| Congenital Erythropoietic Porphyria (CEP) (Gunther Disease ) | 525 | ||
| Porphyria Cutanea Tarda (PCT) | 526 | ||
| Hepatoerythropoietic Porphyria | 527 | ||
| Hereditary Coproporphyria and Variegate Porphyria | 527 | ||
| Erythropoietic Protoporphyria and X-Linked Protoporphyria | 528 | ||
| References | 529 | ||
| Section IX Disorders of Metal Transport and Metabolism | 532 | ||
| 37Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc | 533 | ||
| Copper | 534 | ||
| Wilson Disease | 535 | ||
| Menkes Disease | 537 | ||
| Other Copper Storage Disorders | 538 | ||
| Other Disturbances of Copper Metabolism with a Low Serum Copper | 538 | ||
| Iron | 539 | ||
| Systemic Iron Overload Syndromes (Haemochromatosis ) | 540 | ||
| Iron Deficiency and Distribution Disorders | 541 | ||
| Neurode generation with Brain Iron Accumulation (NBIA) | 542 | ||
| Magnesium | 543 | ||
| Primary Hypomagnesaemia with Secondary Hypocalcaemia | 543 | ||
| Hypomagnesaemia with Hyper-calciuria and Nephrocalcinosis | 544 | ||
| Isolated Dominant Hypomagnesemia | 544 | ||
| Isolated Autosomal Recessive Hypomagnesaemia | 545 | ||
| Manganese | 545 | ||
| Inherited Manganism Due to Mutations in | 545 | ||
| Manganese Transporter Defect | 546 | ||
| Selenium | 546 | ||
| Zinc | 546 | ||
| Acrodermatitis Enteropathica | 547 | ||
| Zinc Deficiency in Breastfed Babies | 548 | ||
| Hyperzincaemia with Hypercalprotectinaemia | 548 | ||
| Autosomal Dominant Hyperzincaemia without Symptoms | 548 | ||
| References | 548 | ||
| Section X Organelle-Related Disorders: Lysosomes, Peroxisomes, and Golgi and Pre-Golgi Systems | 551 | ||
| 38Disorders of Sphingolipid Synthesis, Sphingolipidoses, Niemann-Pick Disease Type C and Neuronal Ceroid Lipofuscinoses | 552 | ||
| Disorders of Sphingolipid Synthesis | 554 | ||
| Serine Palmitoyltransferase (Subunit 1 or 2) Deficiency and HSAN1 | 554 | ||
| Defects in Ceramide Synthases 1 and 2 and Myoclonic Epilepsy | 555 | ||
| Fatty Acid 2-Hydroxylase Deficiency (SPG35/FAHN) | 556 | ||
| GM3 Synthase Deficiency and Amish Epilepsy Syndrome | 556 | ||
| GM2/GD2 Synthase Deficiency (SPG26) | 556 | ||
| Nonlysosomal ß-Glucosidase GBA2 Deficiency : SPG46 and Ataxia | 556 | ||
| Ceramide Synthase 3 and Ultra-Long Chain Fatty Acid .-Hydroxylase (CYP4F22) Deficiencies : Autosomal Recessive Congenital Ichthy | 556 | ||
| Mutations in Ceramide Kinase-Like (CERKL) Gene and Retinal Dystrophy | 557 | ||
| Alkaline Ceramidase 3 (ACER3) Deficiency : Infantile Leukodystrophy | 557 | ||
| Sphingolipidoses | 557 | ||
| Gaucher Disease | 557 | ||
| Acid Sphingomyelinase-Deficient Niemann-Pick Disease (Type A, Type B and Intermediate Forms) | 560 | ||
| GM1 Gangliosidosis | 561 | ||
| GM2 Gangliosidoses | 562 | ||
| Krabbe Disease | 563 | ||
| Metachromatic Leukodystrophy | 564 | ||
| Fabry Disease | 566 | ||
| Farber Disease / Acid Ceramidase Deficiency | 567 | ||
| Prosaposin Deficiency | 567 | ||
| Niemann-Pick Disease Type C | 567 | ||
| Clinical Presentation | 567 | ||
| Metabolic Derangement | 568 | ||
| Genetics | 569 | ||
| Diagnostic Tests | 569 | ||
| Treatment and Prognosis | 569 | ||
| Neuronal Ceroid Lipofuscinoses | 569 | ||
| Clinical Presentation | 569 | ||
| Metabolic Derangement | 571 | ||
| Genetics | 572 | ||
| Diagnostic Tests | 572 | ||
| Treatment and Prognosis | 572 | ||
| Re ferences | 572 | ||
| 39Mucopolysaccharidoses, Oligosaccharidoses and Sialic Acid Disorders | 577 | ||
| Mucopolysaccharidoses | 579 | ||
| Clinical Presentation | 579 | ||
| Metabolic Derangement | 583 | ||
| Genetics | 583 | ||
| Diagnostic Tests | 583 | ||
| Treatment and Prognosis | 583 | ||
| Oligosaccharidoses and Mucolipidoses | 585 | ||
| Clinical Presentation | 585 | ||
| Metabolic Derangements | 587 | ||
| Genetics | 587 | ||
| Diagnostic Tests | 588 | ||
| Treatment and Prognosis | 588 | ||
| References | 588 | ||
| 40Inborn Errors of Non-Mitochondrial Fatty Acid Metabolism Including Peroxisomal Disorders | 591 | ||
| Disorders of Etherphospholipid Biosynthesis | 594 | ||
| Peroxin 7 (PEX7) Deficiency (RCDP Type 1) | 594 | ||
| Glycerone 3-Phosphate Acyltransferase (GNPAT) Deficiency (RCDP type 2) | 594 | ||
| Alkylglycerone 3-Phosphate Synthase (AGPS) Deficiency (RCDP Type 3) | 594 | ||
| PEX5L-Deficiency (RCDP Type 4) | 594 | ||
| Fatty Acyl-CoA Reductase 1 (FAR1) Deficiency | 595 | ||
| Disorders of Peroxisomal ß-Oxidation | 595 | ||
| X-Linked Adrenoleukodystrophy | 595 | ||
| D-Bifunctional Protein (DBP) Deficiency | 596 | ||
| Acyl-CoA Oxidase (ACOX) Deficiency | 597 | ||
| Methyl Acyl-CoA Racemase (AMACR) Deficiency | 597 | ||
| Sterol Carrier Protein-2 (SCPx) Deficiency | 598 | ||
| PMP70 Deficiency | 598 | ||
| Contiguous | 598 | ||
| Syndrome (CADDS) | 598 | ||
| Zellweger Spectrum Disorders (ZSD) | 598 | ||
| Disorders of Peroxisomal Fatty Acid Alpha-Oxidation | 599 | ||
| Adult Refsum Disease (ARD) | 599 | ||
| The Fatty Acid Chain Elongation Disorders | 600 | ||
| ELOVL4 Deficiency | 600 | ||
| ELOVL5 Deficiency | 601 | ||
| Trans-2,3-Enoyl-CoA Reductase (TER) Deficiency | 601 | ||
| 3-Hydroxyacyl-CoA Dehydratase1 (HACD1) Deficiency | 601 | ||
| Disorders of Eicosanoid Metabolism | 601 | ||
| Primary Hypertrophic Osteo-arthropathy Type 1 (PHOAR1): 15-Hydroxy Prostaglandin Dehydrogenase (PGDH) Deficiency and Type 2 (PHO | 601 | ||
| LTC4-Synthase Deficiency | 603 | ||
| Remaining Disorders of Fatty Acid Homeostasis | 603 | ||
| Sjögren Larsson Syndrome (SLS) | 603 | ||
| Bile Acid-CoA: Amino Acid N-Acyltransferase (BAAT) Deficiency | 604 | ||
| Other Peroxisomal Disorders not Involving Fatty Acid Metabolism | 604 | ||
| Oxalurias and Oxalosis: Glyoxylate Detoxification Disorders | 604 | ||
| Pipecolic Acidemia | 604 | ||
| Acatalasemia | 604 | ||
| References | 605 | ||
| 41Congenital Disorders of Glycosylation, Dolichol and Glycosylphosphatidylinositol Metabolism | 607 | ||
| Introduction | 609 | ||
| Congenital Disorders of Protein N-Glycosylation (. Table 41.1) | 611 | ||
| Phosphomannomutase 2 Deficiency (PMM2-CDG) | 611 | ||
| Mannosephosphate Isomerase Deficiency (MPI-CDG) | 612 | ||
| Glucosyltransferase 1 Deficiency (ALG6-CDG) | 612 | ||
| Mannosyltransferase 1 Deficiency (ALG1-CDG) | 613 | ||
| UDP-GlcNAc:Dol-P-GlcNAc-P Trans-ferase Deficiency (DPAGT1-CDG) | 613 | ||
| Golgi a1-2 Mannosidase 1 Deficiency (MAN1B1-CDG) | 614 | ||
| Congenital Disorders of Protein O-Glycosylation (. Table 41.2) | 614 | ||
| Progeroid Variant of Ehlers-Danlos Syndrome (B4GALT7-CDG) | 614 | ||
| GALNT3 Deficiency (GALNT3-CDG) | 614 | ||
| Hereditary Multiple Exostoses (EXT1/EXT2-CDG) | 614 | ||
| Cerebro-Ocular Dysplasia-Muscular Dystrophy Syndromes , Types A1, B1, C1/A2, B2, C2 (POMT1/POMT2-CDG) | 616 | ||
| Muscle-Eye-Brain Disease, Types A3, B3, C3 (POMGNT1-CDG) | 616 | ||
| O-Fucose-Specific ß-1,3-Glucosyl-trans ferase Deficiency (B3GALTL-CDG) | 616 | ||
| Defects in Lipid Glycosylation and in Glycosylphosphatidylinositol (GPI) Anchor Biosynthesis (. Table 41.3) | 616 | ||
| GM3 Synthase Deficiency (ST3GAL5-CDG) | 616 | ||
| GM2 Synthase Deficiency (B4GALNT1-CDG) | 616 | ||
| PIGA Deficiency (PIGA-CDG) | 616 | ||
| Defects in Multiple Glycosylation Pathways and in Other Pathways I ncluding Dolicholphosphate Biosynthesis Defects (. Table 41.4 | 616 | ||
| Hereditary Inclusion Body Myopathy (GNE-CDG) | 616 | ||
| Congenital Myasthenic Syndrome-12 (GFPT1-CDG) | 617 | ||
| Steroid 5-a-Reductase Deficiency (SRD5A3-CDG) | 617 | ||
| COG6 Deficiency (COG6-CDG) | 620 | ||
| Autosomal Recessive Cutis Laxa Type 2 (ATP6V0A2-CDG) | 620 | ||
| Phosphoglucomutase 1 Deficiency (PGM1-CDG) | 620 | ||
| Golgi Homeostasis Disorders: TMEM199 and CCDC115 Deficiencies | 620 | ||
| Manganese and Zinc Transporter Defect : SLC39A8 Deficiency | 620 | ||
| Congenital Disorders of Deglycosylation | 621 | ||
| N-glycanase 1 Deficiency | 621 | ||
| Lysosomal Storage Disorders | 621 | ||
| References | 621 | ||
| 42Cystinosis | 623 | ||
| Infantile Cystinosis | 624 | ||
| Clinical Presentation | 624 | ||
| Metabolic Derangement | 626 | ||
| Genetics | 626 | ||
| Diagnostic Tests | 626 | ||
| Treatment | 626 | ||
| Late-Onset Cystinosis | 627 | ||
| Ocular Cystinosis | 628 | ||
| References | 628 | ||
| Section XI Appendix | 630 | ||
| 43Medications Used in the Treatment of Inborn Errors | 631 | ||
| Subject Index | 640 |