Inborn metabolic diseases: diagnosis and treatment ; with 63 tables
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| Format: | Elektronisch E-Book |
| Sprache: | English |
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Heidelberg
Springer
2006
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| Ausgabe: | 4., rev. ed. |
| Schlagworte: | |
| Online-Zugang: | Volltext Inhaltsverzeichnis |
| Beschreibung: | 1 Online-Ressource |
| ISBN: | 9783540287858 |
| DOI: | 10.1007/978-3-540-28785-8 |
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| 245 | 1 | 0 | |a Inborn metabolic diseases |b diagnosis and treatment ; with 63 tables |c John Fernandes ... (eds.) |
| 250 | |a 4., rev. ed. | ||
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Datensatz im Suchindex
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| adam_text | Contents
I Diagnosis and Treatment:
General Principles
1 A Clinical Approach to Inherited
Metabolic Diseases 3
Jean Marie Saudubray, Isabelle Desguerre,.
Frederic Sedel, Christiane Charpentier
Introduction 5
1.1 Classification of Inborn Errorsof Metabolism .. 5
1.1.1 Pathophysiology 5
1.1.2 Clinical Presentation 6
1.2 Acute Symptoms in the Neonatal Period
and Early Infancy ( 1 Year) 6
1.2.1 Clinical Presentations 6
1.2.2 Metabolic Derangements and Diagnostic
Tests 10
1.3 Later Onset Acute and Recurrent Attacks
(Late Infancy and Beyond) 11
1.3.1 Clinical Presentations 11
1.3.2 Metabolic Derangements and Diagnostic
Tests 19
1.4 Chronic and Progressive General
Symptoms/Signs 24
1.4.1 Gastrointestinal Symptoms 24
1.4.2 Muscle Symptoms 26
1.4.3 Neurological Symptoms 26
1.4.4 Specific Associated Neurological
Abnormalities 33
1.5 Specific Organ Symptoms 39
1.5.1 Cardiology 39
1.5.2 Dermatology 39
1.5.3 Dysmorphology 41
1.5.4 Endocrinology 41
1.5.5 Gastroenterology 42
1.5.6 Hematology 42
1.5.7 Hepatology 43
1.5.8 Immune System 44
1.5.9 Myology 44
1.5.10 Nephrology 45
1.5.11 Neurology 45
1.5.12 Ophthalmology 45
1.5.13 Osteology 46
1.5.14 Pneumology 46
1.5.15 Psychiatry 47
1.5.16 Rheumatology 47
1.5.17 Stomatology 47
1.5.18 Vascular Symptoms 47
References 47
2 Newborn Screening for Inborn Errors
of Metabolism 49
Bridget Wilcken
2.1 Introduction 51
2.2 General Aspects of Newborn Screening 51
2.2.1 Aims and Criteria 51
2.2.2 Sensitivity, Specificity, and Positive Predictive
Value 51
2.2.3 Technical Aspects of Newborn Screening Tests .. 51
2.2.4 Range of Possibilities from Early Detection .... 52
2.2.5 Tandem Mass Spectrometry 52
2.3 Screening for Individual Inborn Errors
of Metabolism 53
2.3.1 Phenylketonuria 53
2.3.2 Galactosaemias 54
2.3.3 Aminoacidopathies 54
2.3.4 Organic Acid Disorders 55
2.3.5 Fatty Acid Oxidation Disorders 55
2.3.6 Other Neonatal Screening Programmes 57
References 57
3 Diagnostic Procedures: Function Tests
and Postmortem Protocol 59
Guy Touati, Jan Huber, Jean Marie Saudubray
3.1 Introduction 61
3.2 Functional Tests 61
3.2.1 Metabolic Profile over the Course of the Day ... 61
3.2.2 Fasting Test 62
3.2.3 Glucose Loading Test 65
3.2.4 Galactose Loading Test 65
3.2.5 Fructose Loading Test 65
3.2.6 Protein and Allopurinol Loading Test 66
3.2.7 Fat Loading Test 66
3.2.8 TetrahydrobiopterinTest 66
3.2.9 Exercise Test 67
3.3 Postmortem Protocol 68
3.3.1 Cells and Tissues for Enzyme Assays 68
3.3.2 Cells and Tissues for Chromosome
and DNA Investigations 68
3.3.3 Skin Fibroblasts 68
3.3.4 Body Fluids for Chemical Investigations 68
3.3.5 Imaging 68
3.3.6 Autopsy 69
References 69
4 Emergency Treatments 71
Viola Prietsch, Helene Ogier de Baulny,
Jean Marie Saudubray
4.1 General Principles 73
4.1.1 Supportive Care 73
4.1.2 Nutrition 73
4.1.3 Specific Therapies 73
4.1.4 Extracorporeal Procedures for Toxin Removal . . 73
4.2 Emergency Management of Particular Clinical
Presentations 74
4.2.1 Neurological Deterioration 74
4.2.2 Liver Failure 77
4.2.3 Neonatal Hypoglycemia 77
4.2.4 Cardiac Failure 78
4.2.5 Primary Hyperlactatemia 78
4.2.6 Intractable Convulsions 78
4.3 Final Considerations 78
References 78
5 Treatment: Present Status
and New Trends 81
John H. Walter, J. Ed Wraith
5.1 Introduction 83
5.2 Reducing the Load on the Affected Pathway ... 83
5.2.1 Substrate Reduction by Dietary Restriction .... 83
5.2.2 Substrate Reduction by Inhibition
of Enzymes Within the Pathway 83
5.3 Correcting Product Deficiency 84
5.3.1 Replenishing Depleted Products 84
5.3.2 Increasing Substrate Supply 84
5.3.3 Providing Alternative Substrates 85
5.4 Decreasing Metabolite Toxicity 85
5.4.1 Removing Toxic Metabolites 85
5.4.2 Blocking the Effects of Toxic Metabolites 85
5.5 Stimulating Residual Enzyme 85
5.5.1 Co Enzyme Treatment 85
5.5.2 Enzyme Enhancement Therapy 86
5.6 Transplantation 87
5.6.1 Hematopoietic Stem Cell Transfer 87
5.6.2 Other Organ Transplantation 87
5.7 Pharmacologic Enzyme Replacement 88
5.7.1 Gaucher Disease 88
5.7.2 Fabry Disease 88
5.7.3 MucopolysaccharidosisTypel 88
5.7.4 MucopolysaccharidosisTypeVI 88
5.7.5 Pompe Disease 88
5.7.6 Other Disorders 88
5.8 GeneTherapy 89
5.8.1 Gene Transfer 89
5.8.2 Pharmacological GeneTherapy 89
5.9 Conclusions 89
References 96
II Disorders of Carbohydrate
Metabolism
6 The Glycogen Storage Diseases
and Related Disorders 101
G. Peter A. Smit, Jan Peter Rake, Hasan O. Akman,
Salvatore DiMauro
6.1 The Liver Glycogenoses 103
6.1.1 Glycogen Storage Disease Type I
(Glucose 6 Phosphatase orTranslocase Deficiency) 103
6.1.2 Glycogen Storage Disease Type III
(Debranching Enzyme Deficiency) 108
6.1.3 Glycogen Storage Disease Type IV
(Branching Enzyme Deficiency) 109
6.1.4 Glycogen Storage Disease Type VI
(Glycogen Phosphorylase Deficiency) 111
6.1.5 Glycogen Storage Disease Type IX
(Phosphorylase Kinase Deficiency) 111
6.1.6 Glycogen Storage Disease Type 0
(Glycogen Synthase Deficiency) 112
6.2 The Muscle Glycogenoses 112
6.2.1 Glycogen Storage Disease Type V
(Myophosphorylase Deficiency) 113
6.2.2 Glycogen Storage Disease Type VII
(Phosphofructokinase Deficiency) 113
6.2.3 Phosphoglycerate Kinase Deficiency 114
6.2.4 Glycogen Storage Disease Type X
(Phosphoglycerate Mutase Deficiency) 114
6.2.5 Glycogen Storage Disease Type XII
(Aldolase A Deficiency) 114
6.2.6 Glycogen Storage Disease Type XIII
(p Enolase Deficiency) 115
6.2.7 Glycogen Storage Disease Type XI
(Lactate Dehydrogenase Deficiency) 115
6.2.8 Muscle Glycogen Storage Disease Type 0
(Glycogen Synthase Deficiency) 115
6.3 The Generalized Glycogenoses and Related
Disorders 115
6.3.1 Glycogen Storage Disease Type II
(Acid Maltase Deficiency) 115
6.3.2 Danon Disease 116
6.3.3 Lafora Disease 116
References 116
7 Disorders of Galactose Metabolism 121
Gerard T. Berry, Stanton Segal, Richard Gitzelmann
7.1 Deficiency of Galactose 1 Phosphate
Uridyltransferase 123
7.1.1 Clinical Presentation 123
7.1.2 Metabolic Derangement 123
7.1.3 Genetics 123
7.1.4 Diagnostic Tests 124
7.1.5 Treatment and Prognosis 124
7.2 Uridine Diphosphate Galactose 4 Epimerase
Deficiency 126
7.2.1 Clinical Presentation 126
7.2.2 Metabolic Derangement 126
7.2.3 Genetics 126
7.2.4 Diagnostic Tests 127
7.2.5 Treatment and Prognosis 127
7.3 Galactokinase Deficiency 127
7.3.1 Clinical Presentation 127
7.3.2 Metabolic Derangement 127
7.3.3 Genetics 127
7.3.4 Diagnostic Tests 127
7.3.5 Treatment and Prognosis 128
7.4 Fanconi Bickel Syndrome 128
7.5 Portosystemic Venous Shunting and Hepatic
Arterio Venous Malformations 128
References 128
8 Disorders of the Pentose Phosphate
Pathway 131
Nanda M. Verhoeven, Cornells Jakobs
8.1 Ribose 5 Phosphate Isomerase Deficiency .... 133
8.1.1 Clinical Presentation 133
8.1.2 Metabolic Derangement 133
8.1.3 Genetics 133
8.1.4 Diagnostic Tests 133
8.1.5 Treatment and Prognosis 133
8.2 Transaldolase Deficiency 133
8.2.1 Clinical Presentation 133
8.2.2 Metabolic Derangement 134
8.2.3 Genetics 134
8.2.4 Diagnostic Tests 134
8.2.5 Treatment and Prognosis 134
References 134
9 Disorders of Fructose Metabolism 135
Beat Steinmann, Rene Santer,
Georges van den Berghe
9.1 Essential Fructosuria 137
9.1.1 Clinical Presentation 137
9.1.2 Metabolic Derangement 137
9.1.3 Genetics 137
9.1.4 Diagnosis 137
9.1.5 Treatment and Prognosis 137
9.2 Hereditary Fructose Intolerance 137
9.2.1 Clinical Presentation 137
9.2.2 Metabolic Derangement 138
9.2.3 Genetics 138
9.2.4 Diagnosis 138
9.2.5 Differential Diagnosis 139
9.2.6 Treatment and Prognosis 139
9.3 Fructose 1,6 Bisphosphatase Deficiency 140
9.3.1 Clinical Presentation 140
9.3.2 Metabolic Derangement 140
9.3.3 Genetics 141
9.3.4 Diagnosis 141
9.3.5 Differential Diagnosis 141
9.3.6 Treatment and Prognosis 141
References 142
10 Persistent Hyperinsulinemic
Hypoglycemia 143
Pascale de Lonlay, Jean Marie Saudubray
10.1 Clinical Presentation 145
10.2 Metabolic Derangement 145
10.3 Genetics 146
10.4 Diagnostic Tests 146
10.4.1 Diagnostic Criteria 146
10.4.2 Differentiation of Focal from Diffuse Forms .... 146
10.5 Treatment and Prognosis 147
10.5.1 Medical Treatment 147
10.5.2 Surgical Treatment 147
10.5.3 Prognosis 147
References 148
11 Disorders of Glucose Transport 151
Reni Santer, JorgKlepper
11.1 Congenital Glucose/Galactose Malabsorption
(SGLT1 Deficiency) 153
11.1.1 Clinical Presentation 153
11.1.2 Metabolic Derangement 153
11.1.3 Genetics 153
11.1.4 Diagnosis 153
11.1.5 Treatment and Prognosis 154
11.2 Renal Glucosuria (SGLT2 Deficiency) 154
11.2.1 Clinical Presentation 154
11.2.2 Metabolic Derangement 154
11.2.3 Genetics 154
11.2.4 Diagnosis 154
11.2.5 Treatment and Prognosis 154
11.3 Glucose Transporter Deficiency Syndrome
(GLUT1 Deficiency) 154
11.3.1 Clinical Presentation 154
11.3.2 Metabolic Derangement 155
11.3.3 Genetics 155
11.3.4 Diagnosis 155
11.3.5 Treatment and Prognosis 155
11.4 Fanconi Bickel Syndrome (GLUT2 Deficiency) .. 155
11.4.1 Clinical Presentation 155
11.4.2 Metabolic Derangement 156
11.4.3 Genetics 156
11.4.4 Diagnosis 156
11.4.5 Treatment and Prognosis 156
References 157
Ill Disorders of Mitochondrial
Energy Metabolism
12 Disorders of Pyruvate Metabolism and the
Tricarboxylic Acid Cycle 161
Linda J. De Meirleir, Rudy Van Coster, Willy Lissens
12.1 Pyruvate Carboxylase Deficiency 163
12.2 Phosphoenolpyruvate Carboxykinase
Deficiency 165
12.3 Pyruvate Dehydrogenase Complex Deficiency. . 167
12.4 Dihydrolipoamide Dehydrogenase Deficiency . . 169
12.5 2 Ketoglutarate Dehydrogenase Complex
Deficiency 169
12.6 Fumarase Deficiency 170
12.7 Succinate Dehydrogenase Deficiency 171
12.8 Pyruvate Transporter Defect 172
References 172
13 Disorders of Mitochondrial Fatty Acid
Oxidation and Related Metabolic Pathways 175
Charles A. Stanley, Michael J. Bennett,
Ertan Mayatepek
13.1 Introduction 177
13.2 Clinical Presentation 177
13.2.1 Camitine Cycle Defects 177
13.2.2 B Oxidation Defects 179
13.2.3 Electron Transfer Defects 180
13.2.4 Ketogenesis Defects 180
13.3 Genetics 180
13.4 Diagnostic Tests 181
13.4.1 Disease Related Metabolites 181
13.4.2 Tests of Overall Pathway 182
13.4.3 Enzyme Assays 183
13.4.4 Prenatal Diagnosis 183
13.5 Treatment and Prognosis 184
13.5.1 Management of Acute Illness 184
13.5.2 Long term Diet Therapy 184
13.5.3 Camitine Therapy 184
13.5.4 Other Therapy 184
13.5.5 Prognosis 185
13.6 RareRelated Disorders 187
13.6.1 Transport Defect of Fatty Acids 187
13.6.2 Defects in Leukotriene Metabolism 187
References 188
14 Disorders of Ketogenesis and Ketolysis .... 191
Andrew A.M. Morris
14.1 Clinical Presentation 193
14.1.1 Mitochondrial 3 Hydroxy 3 Methyl
glutaryl CoA Synthase Deficiency 193
14.1.2 3 Hydroxy 3 Methylglutaryl CoA Lyase
Deficiency 193
14.1.3 Succinyl CoA 3 Oxoacid CoATransferase
Deficiency 193
14.1.4 Mitochondrial Acetoacetyl CoA Thiolase
Deficiency 193
14.2 Metabolic Derangement 194
14.3 Genetics 194
14.4 Diagnostic Tests 194
14.4.1 Mitochondrial 3 Hydroxy 3 Methyl
glutaryl CoA Synthase Deficiency 194
14.4.2 3 Hydroxy 3 Methylglutaryl CoA Lyase
Deficiency 194
14.4.3 Succinyl CoA 3 Oxoacid CoA Transferase
Deficiency 195
14.4.4 Mitochondrial Acetoacetyl CoA Thiolase
Deficiency 195
14.5 Treatment and Prognosis 195
14.6 Cytosolic Acetoacetyl CoA Thiolase Deficiency .. 195
References 196
15 Defects of the Respiratory Chain 197
Arnold Munnich
15.1 Clinical Presentation 199
15.1.1 Fetuses 199
15.1.2 Neonates 199
15.1.3 Infants 201
15.1.4 Children and Adults 201
15.2 Metabolic Derangement 201
15.3 Genetics 202
15.3.1 Mutations in Mitochondrial DNA 203
15.3.2 Mutations in Nuclear DNA 203
15.3.3 Genetic Analysis of Respiratory Chain
Deficiencies 203
15.3.4 Genetic Counseling and Prenatal Diagnosis ... 204
15.4 Diagnostic Tests 204
15.4.1 Screening Tests 204
15.4.2 Enzyme Assays 204
15.4.3 Histopathological Studies 206
15.4.4 Magnetic Resonance Spectroscopy
of Muscle and Brain 207
15.5 Treatment and Prognosis 207
References 208
16 Creatine Deficiency Syndromes 211
Sylvia Stockler Ipsiroglu, Gajja S. Salomons
16.1 Clinical Presentation 213
16.1.1 Guanidinoacetate Methyltransferase
Deficiency 213
16.1.2 Arginine:Glycine Amidinotransferase
Deficiency 213
16.1.3 SLC6A8 Deficiency 213
16.2 Metabolic Derangement 214
16.3 Genetics 214
16.4 Diagnostic Tests 214
16.4.1 MRSofBrain 214
16.4.2 Metabolic Screening 214
16.4.3 DNA Diagnostics 215
16.4.4 Functional Tests/Enzymatic Diagnostics 215
16.4.5 Prenatal Diagnosis 215
16.5 Treatment and Prognosis 215
16.5.1 GAMT Deficiency 215
16.5.2 AGAT Deficiency 216
16.5.3 SLC6A8 Deficiency 216
References 216
IV Disorders of Amino Acid
Metabolism and Transport
17 Hyperphenylalaninaemia 221
John H. Walter, Philip J. Lee, Peter Burgard
17.1 Introduction 223
17.2 Phenylalanine Hydroxylase Deficiency 223
17.2.1 Clinical Presentation 223
17.2.2 Metabolic Derangement 223
17.2.3 Genetics 223
17.2.4 Diagnostic Tests 224
17.2.5 Treatment and Prognosis 224
17.3 Maternal Phenylketonuria 227
17.3.1 Clinical Presentation 227
17.3.2 Metabolic Derangement 227
17.3.3 Management 227
17.3.4 Prognosis 228
17.4 Hyperphenylalaninaemia and Disorders
of Biopterin Metabolism 229
17.4.1 Clinical Presentation 229
17.4.2 Metabolic Derangement 229
17.4.3 Genetics 229
17.4.4 Diagnostic Tests 229
17.4.5 Treatment 230
17.4.6 Outcome 230
References 231
18 Disorders of Tyrosine Metabolism 233
Anupam Chakrapani, Elisabeth Holme
18.1 Hereditary Tyrosinaemia Type I
(Hepatorenal Tyrosinaemia) 235
18.1.1 Clinical Presentation 235
18.1.2 Metabolic Derangement 235
18.1.3 Genetics 236
18.1.4 Diagnostic Tests 236
18.1.5 Treatment and Prognosis 237
18.2 Hereditary Tyrosinaemia Type II
(Oculocutaneous Tyrosinaemia,
Richner Hanhart Syndrome) 238
18.2.1 Clinical Presentation 238
18.2.2 Metabolic Derangement 239
18.2.3 Genetics 239
18.2.4 Diagnostic Tests 239
18.2.5 Treatment and Prognosis 239
18.3 Hereditary Tyrosinaemia Type III 239
18.3.1 Clinical Presentation 239
18.3.2 Metabolic Derangement 239
18.3.3 Genetics 240
18.3.4 Diagnostic Tests 240
18.3.5 Treatment and Prognosis 240
18.4 Transient Tyrosinaemia 240
18.5 Alkaptonuria 240
18.5.1 Clinical Presentation 240
18.5.2 Metabolic Derangement 241
18.5.3 Genetics 241
18.5.4 DiagnosticTests 241
18.5.5 Treatment and Prognosis 241
18.6 Hawkinsinuria 241
18.6.1 Clinical Presentation 241
18.6.2 Metabolic Derangement 241
18.6.3 Genetics 241
18.6.4 DiagnosticTests 241
18.6.5 Treatment and Prognosis 242
References 242
19 Branched Chain Organic
Acidurias/Acidemias 245
Udo Wendel, Hitene Ogier de Baulny
19.1 Maple Syrup Urine Disease, Isovaleric Aciduria,
Propionic Aciduria, Methylmalonic Aciduria . . . 247
19.1.1 Clinical Presentation 247
19.1.2 Metabolic Derangement 249
19.1.3 Genetics 250
19.1.4 DiagnosticTests 251
19.1.5 Treatment and Prognosis 251
19.2 3 Methylcrotonyl Glycinuria 256
19.2.1 Clinical Presentation 256
19.2.2 Metabolic Derangement 256
19.2.3 Genetics 257
19.2.4 DiagnosticTests 257
19.2.5 Treatment and Prognosis 257
19.3 3 Methylglutaconic Aciduria Type I 257
19.4 Short/Branched Chain Acyl CoA Dehydro
genase Deficiency 258
19.5 2 Methyl 3 Hydroxybutyryl CoA Dehydro
genase Deficiency 258
19.6 Isobutyryl CoA Dehydrogenase Deficiency .... 259
19.7 3 Hydroxyisobutyric Aciduria 259
19.8 Malonic Aciduria 259
19.8.1 Clinical Presentation 259
19.8.2 Metabolic Derangement 259
19.8.3 Genetics 259
19.8.4 DiagnosticTests 260
19.8.5 Treatment and Prognosis 260
References 260
20 Disorders of the Urea Cycle
and Related Enzymes 263
lames V. Leonard
20.1 Clinical Presentation 265
20.1.1 Neonatal Presentation 265
20.1.2 Infantile Presentation 265
20.1.3 Children and Adults 265
20.2 Metabolic Derangement 266
20.2.1 The Urea Cycle 266
20.2.2 Toxicity of Ammonia 267
203 Genetics 267
20.4 Diagnostic Tests 268
20.4.1 Biochemical Tests 268
20.4.2 Imaging 268
20.4.3 Differential Diagnosis 268
20.4.4 Prenatal Diagnosis 269
205 Treatment 269
20.5.1 Low Protein Diet 269
20.5.2 Essential Amino Acids 269
20.5.3 Alternative Pathways for Nitrogen Excretion . . . 269
20.5.4 Replacement of Deficient Nutrients 270
20.5.5 General Aspects of Therapy 270
205.6 Emergency Management at Home 270
20.5.7 Emergency Treatment in Hospital 271
20.6 Prognosis 272
References 272
21 Disorders of Sulfur Amino Acid Metabolism 273
Generoso Andria, Brian Fowler,
Gianfranco Sebastio
21.1 Homocystinuria due to Cystathione (J Synthase
Deficiency 275
21.1.1 Clinical Presentation 275
21.1.2 Metabolic Derangement 276
21.1.3 Genetics 276
21.1.4 Diagnostic Tests 277
21.1.5 Treatment and Prognosis 277
21.2 Methionine S Adenosyltransferase Deficiency . 278
21.2.1 Clinical Presentation 278
21.2.2 Metabolic Derangement 278
21.2.3 Genetics 279
21.2.4 Diagnostic Tests 279
21.2.5 Treatment and Prognosis 279
21.3 Glycine N Methyltransferase Deficiency 279
21.3.1 Clinical Presentation 279
21.3.2 Metabolic Derangement 279
21.3.3 Genetics 279
21.3.4 Diagnostic Tests 279
21.3.5 Treatment and Prognosis 279
21.4 S Adenosylhomocysteine Hydrolase Deficiency 279
21.4.1 Clinical Presentation 279
21.4.2 Metabolic Derangement 279
21.4.3 Genetics 280
21.4.4 Diagnostic Tests 280
21.4.5 Treatment and Prognosis 280
21.5 y Cystathionase Deficiency 280
21.5.1 Clinical Presentation 280
21.5.2 Metabolic Derangement 280
21.5.3 Genetics 280
21.5.4 Diagnostic Tests 280
21.5.5 Treatment and Prognosis 280
21.6 Isolated Sulfite Oxidase Deficiency 280
21.6.1 Clinical Presentation 280
21.6.2 Metabolic Derangement 280
21.6.3 Genetics 281
21.6.4 Diagnostic Tests 281
21.6.5 Treatment and Prognosis 281
References 281
22 Disorders of Ornithine Metabolism 283
Vivian E. Shih, Matthias R. Baumgartner
22.1 Hyperornithinemia due to Ornithine Amino
transferase Deficiency (Gyrate Atrophy of
the Choroid and Retina) 285
21.1.1 Clinical Presentation 285
22.1.2 Metabolic Derangement 285
22.1.3 Genetics 286
22.1.4 Diagnostic Tests 286
22.1.5 Treatment and Prognosis 286
22.2 The Hyperornithinemia, Hyperammonemia,
and Homocitrullinuria (HHH) Syndrome 288
21.2.1 Clinical Presentation 288
22.2.2 Metabolic Derangement 288
22.2.3 Genetics 288
22.2.4 Diagnostic Tests 288
22.2.5 Treatment and Prognosis 288
22.3 A1 Pyrroline 5 Carboxylate Synthase Deficiency 289
21.3.1 Clinical Presentation 289
22.3.2 Metabolic Derangement 289
22.3.3 Genetics 289
22.3.4 Diagnostic Tests 289
22.3.5 Treatment and Prognosis 289
References 290
23 Cerebral Organic Acid Disorders and
Other Disorders of Lysine Catabolism 293
Georg E Hoffmann
23.1 Introduction 295
23.2 Hyperlysinemia/Saccharopinuria 295
23.2.1 Clinical Presentation 295
23.2.2 Metabolic Derangement 295
23.2.3 Genetics 296
23.2.4 Diagnostic Tests 296
23.2.5 Treatment and Prognosis 296
23.3 Hydroxylysinuria 296
23.4 2 Amino /2 Oxo Adipic Aciduria 296
23.4.1 Clinical Presentation 296
23.4.2 Metabolic Derangement 296
23.4.3 Genetics 296
23.4.4 Diagnostic Tests 296
23.4.5 Treatment and Prognosis 297
23.5 Glutaric Aciduria Type I (Glutaryl CoA
Dehydrogenase Deficiency) 297
23.5.1 Clinical Presentation 297
23.5.2 Metabolic Derangement 297
23.5.3 Genetics 300
23.5.4 Diagnostic Tests 300
23.5.5 Treatment and Prognosis 301
23.6 L 2 Hydroxyglutaric Aciduria 302
23.6.1 Clinical Presentation 302
23.6.2 Metabolic Derangement 303
23.6.3 Genetics 303
23.6.4 Diagnostic Tests 303
23.6.5 Treatment and Prognosis 303
23.7 D 2 Hydroxyglutaric Aciduria 303
23.7.1 Clinical Presentation 303
23.7.2 Metabolic Derangement 303
23.7.3 Genetics 303
23.7.4 Diagnostic Tests 304
23.7.5 Treatment and Prognosis 304
23.8 N Acetylaspartic Aciduria (Canavan Disease) . . . 304
23.8.1 Clinical Presentation 304
23.8.2 Metabolic Derangement 304
23.8.3 Genetics 304
23.8.4 Diagnostic Tests 304
23.8.5 Treatment and Prognosis 305
References 305
24 Nonketotic Hyperglycinemia
(Glycine Encephalopathy) 307
Olivier Dulac, Marie Odile Rolland
24.1 Clinical Presentation 309
24.1.1 Neonatal NKH 309
24.1.2 LateOnsetNKH 309
24.2 Metabolic Derangement 310
24.3 Genetics 311
24.4 Diagnostic Tests 311
24.5 Differential Diagnosis 311
24.6 Prenatal Diagnosis 312
24.7 Treatment 312
References 312
25 Disorders of Proline and Serine Metabolism 315
Jaak Jaeken
25.1 Inborn Errors of Proline Metabolism 317
25.1.1 Proline Oxidase Deficiency
(HyperprolinemiaTypel) 317
25.1.2 A Pyrroline 5 Carboxylate Dehydrogenase
Deficiency (Hyperprolinemia Type II) 317
25.2 Inborn Errors of Serine Metabolism 318
25.2.1 3 Phosphoglycerate Dehydrogenase Deficiency 318
25.2.2 Phosphoserine Phosphatase Deficiency 318
25.2.3 Serine Deficiency with Ichthyosis and
Polyneuropathy 318
References 319
26 Transport Defects of Amino Acids at the
Cell Membrane: Cystinuria, Lysinuric
Protein Intolerance and Hartnup Disorder. . 321
Kirsti Nanto Salonen, Olli G. Simell
26.1 Cystinuria 323
26.1.1 Clinical Presentation 323
26.1.2 Metabolic Derangement 323
26.1.3 Genetics 323
26.1.4 Diagnostic Tests 323
26.1.5 Treatment and Prognosis 324
26.2 Lysinuric Protein Intolerance 324
26.2.1 Clinical Presentation 324
26.2.2 Metabolic Derangement 325
26.2.3 Genetics 325
26.2.4 DiagnosticTests 325
26.2.5 Treatment and Prognosis 326
26.3 Hartnup Disorder 326
26.3.1 Clinical Presentation 326
26.3.2 Metabolic Derangement 326
26.3.3 Genetics 327
26.3.4 DiagnosticTests 327
26.3.5 Treatment and Prognosis 327
References 327
V Vitamin Responsive Disorders
27 Biotin Responsive Disorders 331
Matthias R. Baumgartner, Terttu Suormala
27.1 Clinical Presentation 333
27.1.1 Holocarboxylase Synthetase Deficiency 333
27.1.2 Biotinidase Deficiency 333
27.1.3 Biotin Responsive Basal Ganglia Disease 334
27.2 Metabolic Derangement 334
27.3 Genetics 334
27.3.1 Holocarboxylase Synthetase Deficiency 334
27.3.2 Biotinidase Deficiency 335
27.3.3 Biotin Responsive Basal Ganglia Disease 335
27.4 DiagnosticTests 335
27.4.1 Holocarboxylase Synthetase Deficiency 335
27.4.2 Biotinidase Deficiency 336
27.4.3 Acquired Biotin Deficiency 336
27.4.4 Prenatal Diagnosis 336
27.5 Treatment and Prognosis 336
27.5.1 Holocarboxylase Synthetase Deficiency 336
27.5.2 Biotinidase Deficiency 336
27.5.3 Biotin Responsive Basal Ganglia Disease 337
References 337
28 Disorders of Cobalamin and Folate
Transport and Metabolism 341
David S. Rosenblatt, Brian Fowler
28.1 Disorders of Absorption and Transport
of Cobalamin 343
28.1.1 Hereditary Intrinsic Factor Deficiency 343
28.1.2 Defective Transport of Cobalamin by Enterocytes
(Imerslund Grasbeck Syndrome) 343
28.1.3 Haptocorrin (R Binder) Deficiency 344
28.1.4 Transcobalamin Deficiency 344
28.2 Disorders of Intracellular Utilization of Cobalamin 345
28.2.1 Combined Deficiencies of Adenosylcobalamin
and Methylcobalamin 345
28.2.2 Adenosylcobalamin Deficiency 347
28.2.3 Methylcobalamin Deficiency 348
28.3 Disorders of Absorption and Metabolism of Folate 351
28.3.1 Hereditary Folate Malabsorption 351
28.3.2 Glutamate Formiminotransferase Deficiency ... 351
28.3.3 Methylenetetrahydrofolate Reductase
Deficiency 352
References 353
VI Neurotransmitter and
Small Peptide Disorders
29 Disorders of Neurotransmission 357
Jaak Jaeken, Cornelis Jakobs, Peter T. Clayton,
Ron A. Wevers
29.1 Inborn Errors of Gamma Amino Butyric
Acid Metabolism 361
29.1.1 Gamma Amino Butyric AcidTransaminase
Deficiency 361
29.1.2 Succinic Semialdehyde Dehydrogenase
Deficiency 362
29.2 Inborn Defects of Receptors and Transporters
ofNeurotransmitters 362
29.2.1 Hyperekplexia 362
29.2.2 GABA Receptor Mutation 363
29.2.3 Mitochondrial Glutamate Transport Defect.... 363
29.3 Inborn Errors of Monoamine Metabolism 365
29.3.1 Tyrosine Hydroxylase Deficiency 365
29.3.2 Aromatic L Aminoacid Decarboxylase Deficiency 365
29.3.3 Dopamine (5 Hydroxylase Deficiency 366
29.3.4 Monoamine Oxidase A Deficiency 366
29.3.5 GuanosineTriphosphate Cyclohydrolase I
Deficiency 367
29.4 Inborn Disorders Involving Pyridoxine
and Pyridoxal Phosphate 369
29.4.1 Pyridoxine Responsive Epilepsy 369
29.4.2 Pyridox(am)ine 5 Phosphate Oxidase
Deficiency 370
References 371
30 Disorders in the Metabolism of Glutathione
and Imidazole Oipeptides 373
Ellinor Ristoff, Agne Larsson, Jaak Jaeken
30.1 Disorders in the Metabolism of Glutathione . . . 375
30.1.1 v Glutamylcysteine Synthetase Deficiency .... 375
30.1.2 Glutathione Synthetase Deficiency 375
30.1.3 Y GlutamylTranspeptidase Deficiency 377
30.1.4 5 Oxoprolinase Deficiency 377
30.1.5 Secondary 5 Oxoprolinuria 377
30.2 Disorders of Imidazole Dipeptides 378
30.2.1 Serum Carnosinase Deficiency 378
30.2.2 Homocarnosinosis 378
30.2.3 Prolidase Deficiency 378
References 379
31 Trimethylaminuria and Dimethylglycine
Dehydrogenase Deficiency 381
Valerie Walker, Ron A. Wevers
31.1 Trimethylaminuria (Fish Odour Syndrome) .... 383
31.1.1 Clinical Presentation 383
31.1.2 Metabolic Derangement 383
31.1.3 Genetics 383
31.1.4 Diagnostic Tests 383
31.1.5 Treatment 383
31.2 Dimethylglycine Dehydrogenase Deficiency ... 384
31.2.1 Clinical Presentation 384
31.2.2 Metabolic Derangement 384
31.2.3 Genetics 384
31.2.4 Diagnostic Tests 384
31.2.5 Treatment 384
References 384
VII Disorders of Lipid and
Bile Acid Metabolism
32 Dyslipidemias 389
Annabelle Rodriguez Oquendo, Peter O. Kwiterovich, Jr.
32.1 Overview of Plasma Lipid and Lipoprotein
Metabolism 391
32.1.1 Exogenous Lipoprotein Metabolism 391
32.1.2 Endogenous Lipoprotein Metabolism 392
32.1.3 Reverse Cholesterol Transport and High Density
Lipoproteins 393
32.1.4 Lipid Lowering Drugs 394
32.2 Disorders of Exogenous Lipoprotein
Metabolism 394
32.2.1 Lipoprotein Lipase Deficiency 394
32.2.2 Apo C ll Deficiency 395
32.3 Disorders of Endogenous Lipoprotein
Metabolism 395
32.3.1 Disorders of VLDL Overproduction 396
32.3.2 Disorders of LDL Removal 397
32.4 Disorders of Endogenous and Exogenous
Lipoprotein Transport 399
32.4.1 Dysbetalipoproteinemia (Type III Hyperlipo
proteinemia) 399
32.4.2 Hepatic Lipase Deficiency 400
32.5 Disorders of Reduced LDL Cholesterol Levels .. 400
32.5.1 Abetalipoproteinemia 400
32.5.2 Hypobetalipoproteinemia 401
32.5.3 Homozygous Hypobetalipoproteinemia 401
32.6 Disorders of Reverse Cholesterol Transport .... 401
32.6.1 Familial Hypoalphalipoproteinemia 401
32.6.2 Apolipoprotein A l Mutations 401
32.6.3 Tangier Disease 402
32.6.4 Lecithin Cholesterol Acyltransferase Deficiency 402
32.6.5 Cholesteryl Ester Transfer Protein Deficiency ... 402
32.6.6 Elevated Lipoprotein (a) 403
32.7 Guidelines for the Clinical Evaluation
and Treatment of Dyslipidemia 403
32.7.1 Clinical Evaluation 403
32.7.2 Dietary Treatment, Weight Reduction
and Exercise 404
32.7.3 Goals for Dietary and Hygienic Therapy 405
32.7.4 Low Density Lipoprotein Lowering Drugs .... 406
32.7.5 Triglyceride Lowering Drugs 407
32.7.6 Combination Pharmacotherapy 408
Abbreviations 408
References 408
33 Disorders of Cholesterol Synthesis 411
Hans R. Waterham, Peter T. Clayton
33.1 Mevalonic Aciduria and Hyper lmmuno
globulinaemia D and Periodic Fever Syndrome
(Mevalonate Kinase Deficiency) 413
33.2 Smith Lemli Opitz Syndrome (7 Dehydro
cholesterol Reductase Deficiency) 414
33.3 X Linked Dominant Chondrodysplasia
Punctata 2 orConradi Hunermann Syndrome
(Sterol A8 A7 Isomerase Deficiency) 415
33.4 CHILD Syndrome (3(3 Hydroxysteroid
C 4 Dehydrogenase Deficiency) 416
33.5 Desmosterolosis (Desmosterol Reductase
Deficiency) 417
33.6 Lathosterolosis (Sterol A5 Desaturase Deficiency) 417
33.7 Hydrops Ectopic Calcification Moth Eaten
(HEM) Skeletal Dysplasia or Greenberg Skeletal
Dysplasia(SterolA14 ReductaseDeficiency) ... 418
33.8 Other Disorders 419
References 419
34 Disorders of Bile Acid Synthesis 421
Peter T. Clayton
34.1 Introduction 423
34.2 3p Hydroxy A5 C27 Steroid Dehydrogenase
Deficiency 423
34.3 A4 3 Oxosteroid 5p Reductase Deficiency 425
34.4 Cerebrotendinous Xanthomatosis
(Sterol 27 Hydroxylase Deficiency) 426
34.5 a Methylacyl CoA Racemase Deficiency 427
34.6 Oxysterol 7a Hydroxylase Deficiency 428
34.7 Bile Acid Amidation Defect 428
34.8 Cholesterol 7a Hydroxylase Deficiency 429
34.9 Disorders of Peroxisome Biogenesis and
Peroxisomal (5 Oxidation 429
References 429
VIII Disorders of Nucleic Acid
and Heme Metabolism
35 Disorders of Purine and Pyrimidine
Metabolism 433
Georges van den Berghe, M. Francoise Vincent,
Sandrine Marie
35.1 Inborn Errors of Purine Metabolism 435
35.1.1 Phosphoribosyl Pyrophosphate Synthetase
Superactivity 435
35.1.2 Adenylosuccinase Deficiency 436
35.1.3 AICA Ribosiduria 437
35.1.4 Muscle AMP Deaminase Deficiency 437
35.1.5 Adenosine Deaminase Deficiency 438
35.1.6 Adenosine Deaminase Superactivity 439
35.1.7 Purine Nucleoside Phosphorylase Deficiency . 440
35.1.8 Xanthine Oxidase Deficiency 440
35.1.9 Hypoxanthine Guanine Phosphoribosyl
transferase Deficiency 441
35.1.10 Adenine Phosphoribosyltransferase Deficiency 442
35.1.11 Deoxyguanosine Kinase Deficiency 442
35.2 Inborn Errors of Pyrimidine Metabolism 445
35.2.1 UMP Synthase Deficiency (Hereditary Orotic
Aciduria) 445
35.2.2 Dihydropyrimidine Dehydrogenase Deficiency 445
35.2.3 Dihydropyrimidinase Deficiency 446
35.2.4 Ureidopropionase Deficiency 446
35.2.5 Pyrimidine 5 Nucleotidase Deficiency 446
35.2.6 Cytosolic 5 Nucleotidase Superactivity 447
35.2.7 Thymidine Phosphorylase Deficiency 447
35.2.8 Thymidine Kinase Deficiency 447
References 447
36 Disorders of Heme Biosynthesis 451
Norman G. Egger, Chul Lee, Karl E. Anderson
36.1 X Linked Sideroblastic Anemia 453
36.2 Classification of Porphyrias 453
36.3 Diagnosis of Porphyrias 454
36.4 5 Aminolevulinic Acid Dehydratase Porphyria 454
36.5 Acute Intermittent Porphyria 455
36.6 Congenital Erythropoietic Porphyria
(Gunther Disease) 458
36.7 PorphyriaCutaneaTarda 459
36.8 Hepatoerythropoietic Porphyria 460
36.9 Hereditary Coproporphyria and Variegate
Porphyria 461
36.10 Erythropoietic Protoporphyria 462
References 463
IX Disorders of Metal Transport
37 Disorders in the Transport of Copper, Zinc
and Magnesium 467
Roderick H.J. Houwen
37.1 Copper 469
37.1.1 Wilson Disease 469
37.1.2 Menkes Disease 471
37.1.3 Other Copper Storage Disorders 472
37.2 Zinc 472
37.2.1 Acrodermatitis Enteropathica 472
37.2.2 Zink Deficiency in Breastfed Babies 473
37.2.3 Hyperzincemia with Hypercalprotectinemia . . . 473
37.2.4 Autosomal Dominant Hyperzincemia Without
Symptoms 473
37.3 Magnesium 474
37.3.1 Primary Hypomagnesemia with Secondary
Hypocalcemia 474
37.3.2 Hypomagnesemia with Hypercalciuria and
Nephrocalcinosis 474
37.3.3 Isolated Dominant Hypomagnesemia 475
37.3.4 Isolated Autosomal Recessive Hypomagnesemia 475
37.3.5 OtherMetals 475
References 475
X Organelle Related Disorders:
Lysosomes, Peroxisomes, and
Golgi and Pre Golgi Systems
38 Disorders of Sphingolipid Metabolism .... 479
Marie Therese Vanier
38.1 Gaucher Disease 481
38.2 Niemann PickDiseaseTypeAandB 482
38.3 GMI Gangliosidosis 484
38.4 GM2 Gangliosidoses 485
38.5 Krabbe Disease 486
38.6 Metachromatic Leukodystrophy 487
38.7 Fabry Disease 489
38.8 Farber Disease 490
38.9 Prosaposin Deficiency 490
38.10 Niemann Pick Disease Type C 491
References 492
39 Mucopolysaccharidoses and Oligo
saccharidoses 495
/. Ed Wraith
39.1 Clinical Presentation 497
39.1.1 Mucopolysaccharidoses 497
39.1.2 Oligosaccharidoses 505
39.2 Metabolic Derangements 506
39.3 Genetics 506
39.4 Diagnostic Tests 506
39.5 Treatment and Prognosis 506
References 507
40 Peroxisomal Disorders 509
Bwee Tien Poll The, Patrick Aubourg,
Ronald J.A. Wanders
40.1 Clinical Presentation 511
40.1.1 Dysmorphism 511
40.1.2 Neurological Dysfunction 512
40.1.3 Hepatic and Gastrointestinal Disease 512
40.2 Metabolic Derangements 514
40.2.1 Peroxisome Biogenesis 514
40.2.2 Metabolic Functions of Peroxisomes 515
40.2.3 Metabolic Abnormalities in the Different
Peroxisomal Disorders 518
40.3 Genetics 519
40.4 Diagnostic Tests 519
40.4.1 Diagnostic Group 1 519
40.4.2 Diagnostic Group 2 519
40.4.3 Diagnostic Group 3 519
40.4.4 Diagnostic Group 4 520
40.4.5 Histological Detection 520
40.4.6 Prenatal Diagnosis 520
40.5 Treatment and Prognosis 520
References 521
41 Congenital Disorders of Glycosylation .... 523
Jaakjaeken
41.1 Introduction 525
41.2 Congenital Disorders of Protein N Glyco
sylation 526
41.2.1 Phosphomannomutase 2 Deficiency (CDG la) . . 526
41.2.2 Phosphomannose lsomerase Deficiency
(CDG lb) 527
41.2.3 Glucosyltransferase I Deficiency (CDG lc) 528
41.3 Congenital Disorders of Protein O Glyco
sylation 528
41.3.1 Hereditary Multiple Exostoses 528
41.3.2 Walker Warburg Syndrome 529
41.3.3 Muscle Eye Brain Disease 529
41.4 Newly Discovered Disorders 529
41.4.1 COG7 Deficiency 529
41.4.2 GM3 Synthase Deficiency 529
References 530
42 Cystinosis 531
Michel Broyer
42.1 Infantile Cystinosis 533
42.1.1 Clinical Presentation 533
42.1.2 Metabolic Derangement 534
42.1.3 Genetics 535
42.1.4 Diagnostic Tests 535
42.1.5 Treatment 535
42.2 Adolescent Cystinosis 536
42.3 Adult Benign Cystinosis 536
References 536
43 Primary Hyperoxalurias 539
Pierre Cochat, Marie Odile Rolland
43.1 Primary Hyperoxaluria Type 1 541
43.1.1 Clinical Presentation 541
43.1.2 Metabolic Derangement 542
43.1.3 Genetics 542
43.1.4 Diagnosis 542
43.1.5 Treatment and Prognosis 542
43.2 Primary Hyperoxaluria Type 2 545
43.2.1 Clinical Presentation 545
43.2.2 Metabolic Derangement 545
43.2.3 Genetics 545
43.2.4 Diagnosis 545
43.2.5 Treatment and Prognosis 545
43.3 Non Type 1 Non Type 2 Primary Hyperoxaluria . . 545
References 545
Subject Index 547
|
| adam_txt |
Contents
I Diagnosis and Treatment:
General Principles
1 A Clinical Approach to Inherited
Metabolic Diseases 3
Jean Marie Saudubray, Isabelle Desguerre,.
Frederic Sedel, Christiane Charpentier
Introduction 5
1.1 Classification of Inborn Errorsof Metabolism . 5
1.1.1 Pathophysiology 5
1.1.2 Clinical Presentation 6
1.2 Acute Symptoms in the Neonatal Period
and Early Infancy ( 1 Year) 6
1.2.1 Clinical Presentations 6
1.2.2 Metabolic Derangements and Diagnostic
Tests 10
1.3 Later Onset Acute and Recurrent Attacks
(Late Infancy and Beyond) 11
1.3.1 Clinical Presentations 11
1.3.2 Metabolic Derangements and Diagnostic
Tests 19
1.4 Chronic and Progressive General
Symptoms/Signs 24
1.4.1 Gastrointestinal Symptoms 24
1.4.2 Muscle Symptoms 26
1.4.3 Neurological Symptoms 26
1.4.4 Specific Associated Neurological
Abnormalities 33
1.5 Specific Organ Symptoms 39
1.5.1 Cardiology 39
1.5.2 Dermatology 39
1.5.3 Dysmorphology 41
1.5.4 Endocrinology 41
1.5.5 Gastroenterology 42
1.5.6 Hematology 42
1.5.7 Hepatology 43
1.5.8 Immune System 44
1.5.9 Myology 44
1.5.10 Nephrology 45
1.5.11 Neurology 45
1.5.12 Ophthalmology 45
1.5.13 Osteology 46
1.5.14 Pneumology 46
1.5.15 Psychiatry 47
1.5.16 Rheumatology 47
1.5.17 Stomatology 47
1.5.18 Vascular Symptoms 47
References 47
2 Newborn Screening for Inborn Errors
of Metabolism 49
Bridget Wilcken
2.1 Introduction 51
2.2 General Aspects of Newborn Screening 51
2.2.1 Aims and Criteria 51
2.2.2 Sensitivity, Specificity, and Positive Predictive
Value 51
2.2.3 Technical Aspects of Newborn Screening Tests . 51
2.2.4 Range of Possibilities from Early Detection . 52
2.2.5 Tandem Mass Spectrometry 52
2.3 Screening for Individual Inborn Errors
of Metabolism 53
2.3.1 Phenylketonuria 53
2.3.2 Galactosaemias 54
2.3.3 Aminoacidopathies 54
2.3.4 Organic Acid Disorders 55
2.3.5 Fatty Acid Oxidation Disorders 55
2.3.6 Other Neonatal Screening Programmes 57
References 57
3 Diagnostic Procedures: Function Tests
and Postmortem Protocol 59
Guy Touati, Jan Huber, Jean Marie Saudubray
3.1 Introduction 61
3.2 Functional Tests 61
3.2.1 Metabolic Profile over the Course of the Day . 61
3.2.2 Fasting Test 62
3.2.3 Glucose Loading Test 65
3.2.4 Galactose Loading Test 65
3.2.5 Fructose Loading Test 65
3.2.6 Protein and Allopurinol Loading Test 66
3.2.7 Fat Loading Test 66
3.2.8 TetrahydrobiopterinTest 66
3.2.9 Exercise Test 67
3.3 Postmortem Protocol 68
3.3.1 Cells and Tissues for Enzyme Assays 68
3.3.2 Cells and Tissues for Chromosome
and DNA Investigations 68
3.3.3 Skin Fibroblasts 68
3.3.4 Body Fluids for Chemical Investigations 68
3.3.5 Imaging 68
3.3.6 Autopsy 69
References 69
4 Emergency Treatments 71
Viola Prietsch, Helene Ogier de Baulny,
Jean Marie Saudubray
4.1 General Principles 73
4.1.1 Supportive Care 73
4.1.2 Nutrition 73
4.1.3 Specific Therapies 73
4.1.4 Extracorporeal Procedures for Toxin Removal . . 73
4.2 Emergency Management of Particular Clinical
Presentations 74
4.2.1 Neurological Deterioration 74
4.2.2 Liver Failure 77
4.2.3 Neonatal Hypoglycemia 77
4.2.4 Cardiac Failure 78
4.2.5 Primary Hyperlactatemia 78
4.2.6 Intractable Convulsions 78
4.3 Final Considerations 78
References 78
5 Treatment: Present Status
and New Trends 81
John H. Walter, J. Ed Wraith
5.1 Introduction 83
5.2 Reducing the Load on the Affected Pathway . 83
5.2.1 Substrate Reduction by Dietary Restriction . 83
5.2.2 Substrate Reduction by Inhibition
of Enzymes Within the Pathway 83
5.3 Correcting Product Deficiency 84
5.3.1 Replenishing Depleted Products 84
5.3.2 Increasing Substrate Supply 84
5.3.3 Providing Alternative Substrates 85
5.4 Decreasing Metabolite Toxicity 85
5.4.1 Removing Toxic Metabolites 85
5.4.2 Blocking the Effects of Toxic Metabolites 85
5.5 Stimulating Residual Enzyme 85
5.5.1 Co Enzyme Treatment 85
5.5.2 Enzyme Enhancement Therapy 86
5.6 Transplantation 87
5.6.1 Hematopoietic Stem Cell Transfer 87
5.6.2 Other Organ Transplantation 87
5.7 Pharmacologic Enzyme Replacement 88
5.7.1 Gaucher Disease 88
5.7.2 Fabry Disease 88
5.7.3 MucopolysaccharidosisTypel 88
5.7.4 MucopolysaccharidosisTypeVI 88
5.7.5 Pompe Disease 88
5.7.6 Other Disorders 88
5.8 GeneTherapy 89
5.8.1 Gene Transfer 89
5.8.2 Pharmacological GeneTherapy 89
5.9 Conclusions 89
References 96
II Disorders of Carbohydrate
Metabolism
6 The Glycogen Storage Diseases
and Related Disorders 101
G. Peter A. Smit, Jan Peter Rake, Hasan O. Akman,
Salvatore DiMauro
6.1 The Liver Glycogenoses 103
6.1.1 Glycogen Storage Disease Type I
(Glucose 6 Phosphatase orTranslocase Deficiency) 103
6.1.2 Glycogen Storage Disease Type III
(Debranching Enzyme Deficiency) 108
6.1.3 Glycogen Storage Disease Type IV
(Branching Enzyme Deficiency) 109
6.1.4 Glycogen Storage Disease Type VI
(Glycogen Phosphorylase Deficiency) 111
6.1.5 Glycogen Storage Disease Type IX
(Phosphorylase Kinase Deficiency) 111
6.1.6 Glycogen Storage Disease Type 0
(Glycogen Synthase Deficiency) 112
6.2 The Muscle Glycogenoses 112
6.2.1 Glycogen Storage Disease Type V
(Myophosphorylase Deficiency) 113
6.2.2 Glycogen Storage Disease Type VII
(Phosphofructokinase Deficiency) 113
6.2.3 Phosphoglycerate Kinase Deficiency 114
6.2.4 Glycogen Storage Disease Type X
(Phosphoglycerate Mutase Deficiency) 114
6.2.5 Glycogen Storage Disease Type XII
(Aldolase A Deficiency) 114
6.2.6 Glycogen Storage Disease Type XIII
(p Enolase Deficiency) 115
6.2.7 Glycogen Storage Disease Type XI
(Lactate Dehydrogenase Deficiency) 115
6.2.8 Muscle Glycogen Storage Disease Type 0
(Glycogen Synthase Deficiency) 115
6.3 The Generalized Glycogenoses and Related
Disorders 115
6.3.1 Glycogen Storage Disease Type II
(Acid Maltase Deficiency) 115
6.3.2 Danon Disease 116
6.3.3 Lafora Disease 116
References 116
7 Disorders of Galactose Metabolism 121
Gerard T. Berry, Stanton Segal, Richard Gitzelmann
7.1 Deficiency of Galactose 1 Phosphate
Uridyltransferase 123
7.1.1 Clinical Presentation 123
7.1.2 Metabolic Derangement 123
7.1.3 Genetics 123
7.1.4 Diagnostic Tests 124
7.1.5 Treatment and Prognosis 124
7.2 Uridine Diphosphate Galactose 4' Epimerase
Deficiency 126
7.2.1 Clinical Presentation 126
7.2.2 Metabolic Derangement 126
7.2.3 Genetics 126
7.2.4 Diagnostic Tests 127
7.2.5 Treatment and Prognosis 127
7.3 Galactokinase Deficiency 127
7.3.1 Clinical Presentation 127
7.3.2 Metabolic Derangement 127
7.3.3 Genetics 127
7.3.4 Diagnostic Tests 127
7.3.5 Treatment and Prognosis 128
7.4 Fanconi Bickel Syndrome 128
7.5 Portosystemic Venous Shunting and Hepatic
Arterio Venous Malformations 128
References 128
8 Disorders of the Pentose Phosphate
Pathway 131
Nanda M. Verhoeven, Cornells Jakobs
8.1 Ribose 5 Phosphate Isomerase Deficiency . 133
8.1.1 Clinical Presentation 133
8.1.2 Metabolic Derangement 133
8.1.3 Genetics 133
8.1.4 Diagnostic Tests 133
8.1.5 Treatment and Prognosis 133
8.2 Transaldolase Deficiency 133
8.2.1 Clinical Presentation 133
8.2.2 Metabolic Derangement 134
8.2.3 Genetics 134
8.2.4 Diagnostic Tests 134
8.2.5 Treatment and Prognosis 134
References 134
9 Disorders of Fructose Metabolism 135
Beat Steinmann, Rene Santer,
Georges van den Berghe
9.1 Essential Fructosuria 137
9.1.1 Clinical Presentation 137
9.1.2 Metabolic Derangement 137
9.1.3 Genetics 137
9.1.4 Diagnosis 137
9.1.5 Treatment and Prognosis 137
9.2 Hereditary Fructose Intolerance 137
9.2.1 Clinical Presentation 137
9.2.2 Metabolic Derangement 138
9.2.3 Genetics 138
9.2.4 Diagnosis 138
9.2.5 Differential Diagnosis 139
9.2.6 Treatment and Prognosis 139
9.3 Fructose 1,6 Bisphosphatase Deficiency 140
9.3.1 Clinical Presentation 140
9.3.2 Metabolic Derangement 140
9.3.3 Genetics 141
9.3.4 Diagnosis 141
9.3.5 Differential Diagnosis 141
9.3.6 Treatment and Prognosis 141
References 142
10 Persistent Hyperinsulinemic
Hypoglycemia 143
Pascale de Lonlay, Jean Marie Saudubray
10.1 Clinical Presentation 145
10.2 Metabolic Derangement 145
10.3 Genetics 146
10.4 Diagnostic Tests 146
10.4.1 Diagnostic Criteria 146
10.4.2 Differentiation of Focal from Diffuse Forms . 146
10.5 Treatment and Prognosis 147
10.5.1 Medical Treatment 147
10.5.2 Surgical Treatment 147
10.5.3 Prognosis 147
References 148
11 Disorders of Glucose Transport 151
Reni Santer, JorgKlepper
11.1 Congenital Glucose/Galactose Malabsorption
(SGLT1 Deficiency) 153
11.1.1 Clinical Presentation 153
11.1.2 Metabolic Derangement 153
11.1.3 Genetics 153
11.1.4 Diagnosis 153
11.1.5 Treatment and Prognosis 154
11.2 Renal Glucosuria (SGLT2 Deficiency) 154
11.2.1 Clinical Presentation 154
11.2.2 Metabolic Derangement 154
11.2.3 Genetics 154
11.2.4 Diagnosis 154
11.2.5 Treatment and Prognosis 154
11.3 Glucose Transporter Deficiency Syndrome
(GLUT1 Deficiency) 154
11.3.1 Clinical Presentation 154
11.3.2 Metabolic Derangement 155
11.3.3 Genetics 155
11.3.4 Diagnosis 155
11.3.5 Treatment and Prognosis 155
11.4 Fanconi Bickel Syndrome (GLUT2 Deficiency) . 155
11.4.1 Clinical Presentation 155
11.4.2 Metabolic Derangement 156
11.4.3 Genetics 156
11.4.4 Diagnosis 156
11.4.5 Treatment and Prognosis 156
References 157
Ill Disorders of Mitochondrial
Energy Metabolism
12 Disorders of Pyruvate Metabolism and the
Tricarboxylic Acid Cycle 161
Linda J. De Meirleir, Rudy Van Coster, Willy Lissens
12.1 Pyruvate Carboxylase Deficiency 163
12.2 Phosphoenolpyruvate Carboxykinase
Deficiency 165
12.3 Pyruvate Dehydrogenase Complex Deficiency. . 167
12.4 Dihydrolipoamide Dehydrogenase Deficiency . . 169
12.5 2 Ketoglutarate Dehydrogenase Complex
Deficiency 169
12.6 Fumarase Deficiency 170
12.7 Succinate Dehydrogenase Deficiency 171
12.8 Pyruvate Transporter Defect 172
References 172
13 Disorders of Mitochondrial Fatty Acid
Oxidation and Related Metabolic Pathways 175
Charles A. Stanley, Michael J. Bennett,
Ertan Mayatepek
13.1 Introduction 177
13.2 Clinical Presentation 177
13.2.1 Camitine Cycle Defects 177
13.2.2 B Oxidation Defects 179
13.2.3 Electron Transfer Defects 180
13.2.4 Ketogenesis Defects 180
13.3 Genetics 180
13.4 Diagnostic Tests 181
13.4.1 Disease Related Metabolites 181
13.4.2 Tests of Overall Pathway 182
13.4.3 Enzyme Assays 183
13.4.4 Prenatal Diagnosis 183
13.5 Treatment and Prognosis 184
13.5.1 Management of Acute Illness 184
13.5.2 Long term Diet Therapy 184
13.5.3 Camitine Therapy 184
13.5.4 Other Therapy 184
13.5.5 Prognosis 185
13.6 RareRelated Disorders 187
13.6.1 Transport Defect of Fatty Acids 187
13.6.2 Defects in Leukotriene Metabolism 187
References 188
14 Disorders of Ketogenesis and Ketolysis . 191
Andrew A.M. Morris
14.1 Clinical Presentation 193
14.1.1 Mitochondrial 3 Hydroxy 3 Methyl
glutaryl CoA Synthase Deficiency 193
14.1.2 3 Hydroxy 3 Methylglutaryl CoA Lyase
Deficiency 193
14.1.3 Succinyl CoA 3 Oxoacid CoATransferase
Deficiency 193
14.1.4 Mitochondrial Acetoacetyl CoA Thiolase
Deficiency 193
14.2 Metabolic Derangement 194
14.3 Genetics 194
14.4 Diagnostic Tests 194
14.4.1 Mitochondrial 3 Hydroxy 3 Methyl
glutaryl CoA Synthase Deficiency 194
14.4.2 3 Hydroxy 3 Methylglutaryl CoA Lyase
Deficiency 194
14.4.3 Succinyl CoA 3 Oxoacid CoA Transferase
Deficiency 195
14.4.4 Mitochondrial Acetoacetyl CoA Thiolase
Deficiency 195
14.5 Treatment and Prognosis 195
14.6 Cytosolic Acetoacetyl CoA Thiolase Deficiency . 195
References 196
15 Defects of the Respiratory Chain 197
Arnold Munnich
15.1 Clinical Presentation 199
15.1.1 Fetuses 199
15.1.2 Neonates 199
15.1.3 Infants 201
15.1.4 Children and Adults 201
15.2 Metabolic Derangement 201
15.3 Genetics 202
15.3.1 Mutations in Mitochondrial DNA 203
15.3.2 Mutations in Nuclear DNA 203
15.3.3 Genetic Analysis of Respiratory Chain
Deficiencies 203
15.3.4 Genetic Counseling and Prenatal Diagnosis . 204
15.4 Diagnostic Tests 204
15.4.1 Screening Tests 204
15.4.2 Enzyme Assays 204
15.4.3 Histopathological Studies 206
15.4.4 Magnetic Resonance Spectroscopy
of Muscle and Brain 207
15.5 Treatment and Prognosis 207
References 208
16 Creatine Deficiency Syndromes 211
Sylvia Stockler Ipsiroglu, Gajja S. Salomons
16.1 Clinical Presentation 213
16.1.1 Guanidinoacetate Methyltransferase
Deficiency 213
16.1.2 Arginine:Glycine Amidinotransferase
Deficiency 213
16.1.3 SLC6A8 Deficiency 213
16.2 Metabolic Derangement 214
16.3 Genetics 214
16.4 Diagnostic Tests 214
16.4.1 MRSofBrain 214
16.4.2 Metabolic Screening 214
16.4.3 DNA Diagnostics 215
16.4.4 Functional Tests/Enzymatic Diagnostics 215
16.4.5 Prenatal Diagnosis 215
16.5 Treatment and Prognosis 215
16.5.1 GAMT Deficiency 215
16.5.2 AGAT Deficiency 216
16.5.3 SLC6A8 Deficiency 216
References 216
IV Disorders of Amino Acid
Metabolism and Transport
17 Hyperphenylalaninaemia 221
John H. Walter, Philip J. Lee, Peter Burgard
17.1 Introduction 223
17.2 Phenylalanine Hydroxylase Deficiency 223
17.2.1 Clinical Presentation 223
17.2.2 Metabolic Derangement 223
17.2.3 Genetics 223
17.2.4 Diagnostic Tests 224
17.2.5 Treatment and Prognosis 224
17.3 Maternal Phenylketonuria 227
17.3.1 Clinical Presentation 227
17.3.2 Metabolic Derangement 227
17.3.3 Management 227
17.3.4 Prognosis 228
17.4 Hyperphenylalaninaemia and Disorders
of Biopterin Metabolism 229
17.4.1 Clinical Presentation 229
17.4.2 Metabolic Derangement 229
17.4.3 Genetics 229
17.4.4 Diagnostic Tests 229
17.4.5 Treatment 230
17.4.6 Outcome 230
References 231
18 Disorders of Tyrosine Metabolism 233
Anupam Chakrapani, Elisabeth Holme
18.1 Hereditary Tyrosinaemia Type I
(Hepatorenal Tyrosinaemia) 235
18.1.1 Clinical Presentation 235
18.1.2 Metabolic Derangement 235
18.1.3 Genetics 236
18.1.4 Diagnostic Tests 236
18.1.5 Treatment and Prognosis 237
18.2 Hereditary Tyrosinaemia Type II
(Oculocutaneous Tyrosinaemia,
Richner Hanhart Syndrome) 238
18.2.1 Clinical Presentation 238
18.2.2 Metabolic Derangement 239
18.2.3 Genetics 239
18.2.4 Diagnostic Tests 239
18.2.5 Treatment and Prognosis 239
18.3 Hereditary Tyrosinaemia Type III 239
18.3.1 Clinical Presentation 239
18.3.2 Metabolic Derangement 239
18.3.3 Genetics 240
18.3.4 Diagnostic Tests 240
18.3.5 Treatment and Prognosis 240
18.4 Transient Tyrosinaemia 240
18.5 Alkaptonuria 240
18.5.1 Clinical Presentation 240
18.5.2 Metabolic Derangement 241
18.5.3 Genetics 241
18.5.4 DiagnosticTests 241
18.5.5 Treatment and Prognosis 241
18.6 Hawkinsinuria 241
18.6.1 Clinical Presentation 241
18.6.2 Metabolic Derangement 241
18.6.3 Genetics 241
18.6.4 DiagnosticTests 241
18.6.5 Treatment and Prognosis 242
References 242
19 Branched Chain Organic
Acidurias/Acidemias 245
Udo Wendel, Hitene Ogier de Baulny
19.1 Maple Syrup Urine Disease, Isovaleric Aciduria,
Propionic Aciduria, Methylmalonic Aciduria . . . 247
19.1.1 Clinical Presentation 247
19.1.2 Metabolic Derangement 249
19.1.3 Genetics 250
19.1.4 DiagnosticTests 251
19.1.5 Treatment and Prognosis 251
19.2 3 Methylcrotonyl Glycinuria 256
19.2.1 Clinical Presentation 256
19.2.2 Metabolic Derangement 256
19.2.3 Genetics 257
19.2.4 DiagnosticTests 257
19.2.5 Treatment and Prognosis 257
19.3 3 Methylglutaconic Aciduria Type I 257
19.4 Short/Branched Chain Acyl CoA Dehydro
genase Deficiency 258
19.5 2 Methyl 3 Hydroxybutyryl CoA Dehydro
genase Deficiency 258
19.6 Isobutyryl CoA Dehydrogenase Deficiency . 259
19.7 3 Hydroxyisobutyric Aciduria 259
19.8 Malonic Aciduria 259
19.8.1 Clinical Presentation 259
19.8.2 Metabolic Derangement 259
19.8.3 Genetics 259
19.8.4 DiagnosticTests 260
19.8.5 Treatment and Prognosis 260
References 260
20 Disorders of the Urea Cycle
and Related Enzymes 263
lames V. Leonard
20.1 Clinical Presentation 265
20.1.1 Neonatal Presentation 265
20.1.2 Infantile Presentation 265
20.1.3 Children and Adults 265
20.2 Metabolic Derangement 266
20.2.1 The Urea Cycle 266
20.2.2 Toxicity of Ammonia 267
203 Genetics 267
20.4 Diagnostic Tests 268
20.4.1 Biochemical Tests 268
20.4.2 Imaging 268
20.4.3 Differential Diagnosis 268
20.4.4 Prenatal Diagnosis 269
205 Treatment 269
20.5.1 Low Protein Diet 269
20.5.2 Essential Amino Acids 269
20.5.3 Alternative Pathways for Nitrogen Excretion . . . 269
20.5.4 Replacement of Deficient Nutrients 270
20.5.5 General Aspects of Therapy 270
205.6 Emergency Management at Home 270
20.5.7 Emergency Treatment in Hospital 271
20.6 Prognosis 272
References 272
21 Disorders of Sulfur Amino Acid Metabolism 273
Generoso Andria, Brian Fowler,
Gianfranco Sebastio
21.1 Homocystinuria due to Cystathione (J Synthase
Deficiency 275
21.1.1 Clinical Presentation 275
21.1.2 Metabolic Derangement 276
21.1.3 Genetics 276
21.1.4 Diagnostic Tests 277
21.1.5 Treatment and Prognosis 277
21.2 Methionine S Adenosyltransferase Deficiency . 278
21.2.1 Clinical Presentation 278
21.2.2 Metabolic Derangement 278
21.2.3 Genetics 279
21.2.4 Diagnostic Tests 279
21.2.5 Treatment and Prognosis 279
21.3 Glycine N Methyltransferase Deficiency 279
21.3.1 Clinical Presentation 279
21.3.2 Metabolic Derangement 279
21.3.3 Genetics 279
21.3.4 Diagnostic Tests 279
21.3.5 Treatment and Prognosis 279
21.4 S Adenosylhomocysteine Hydrolase Deficiency 279
21.4.1 Clinical Presentation 279
21.4.2 Metabolic Derangement 279
21.4.3 Genetics 280
21.4.4 Diagnostic Tests 280
21.4.5 Treatment and Prognosis 280
21.5 y Cystathionase Deficiency 280
21.5.1 Clinical Presentation 280
21.5.2 Metabolic Derangement 280
21.5.3 Genetics 280
21.5.4 Diagnostic Tests 280
21.5.5 Treatment and Prognosis 280
21.6 Isolated Sulfite Oxidase Deficiency 280
21.6.1 Clinical Presentation 280
21.6.2 Metabolic Derangement 280
21.6.3 Genetics 281
21.6.4 Diagnostic Tests 281
21.6.5 Treatment and Prognosis 281
References 281
22 Disorders of Ornithine Metabolism 283
Vivian E. Shih, Matthias R. Baumgartner
22.1 Hyperornithinemia due to Ornithine Amino
transferase Deficiency (Gyrate Atrophy of
the Choroid and Retina) 285
21.1.1 Clinical Presentation 285
22.1.2 Metabolic Derangement 285
22.1.3 Genetics 286
22.1.4 Diagnostic Tests 286
22.1.5 Treatment and Prognosis 286
22.2 The Hyperornithinemia, Hyperammonemia,
and Homocitrullinuria (HHH) Syndrome 288
21.2.1 Clinical Presentation 288
22.2.2 Metabolic Derangement 288
22.2.3 Genetics 288
22.2.4 Diagnostic Tests 288
22.2.5 Treatment and Prognosis 288
22.3 A1 Pyrroline 5 Carboxylate Synthase Deficiency 289
21.3.1 Clinical Presentation 289
22.3.2 Metabolic Derangement 289
22.3.3 Genetics 289
22.3.4 Diagnostic Tests 289
22.3.5 Treatment and Prognosis 289
References 290
23 Cerebral Organic Acid Disorders and
Other Disorders of Lysine Catabolism 293
Georg E Hoffmann
23.1 Introduction 295
23.2 Hyperlysinemia/Saccharopinuria 295
23.2.1 Clinical Presentation 295
23.2.2 Metabolic Derangement 295
23.2.3 Genetics 296
23.2.4 Diagnostic Tests 296
23.2.5 Treatment and Prognosis 296
23.3 Hydroxylysinuria 296
23.4 2 Amino /2 Oxo Adipic Aciduria 296
23.4.1 Clinical Presentation 296
23.4.2 Metabolic Derangement 296
23.4.3 Genetics 296
23.4.4 Diagnostic Tests 296
23.4.5 Treatment and Prognosis 297
23.5 Glutaric Aciduria Type I (Glutaryl CoA
Dehydrogenase Deficiency) 297
23.5.1 Clinical Presentation 297
23.5.2 Metabolic Derangement 297
23.5.3 Genetics 300
23.5.4 Diagnostic Tests 300
23.5.5 Treatment and Prognosis 301
23.6 L 2 Hydroxyglutaric Aciduria 302
23.6.1 Clinical Presentation 302
23.6.2 Metabolic Derangement 303
23.6.3 Genetics 303
23.6.4 Diagnostic Tests 303
23.6.5 Treatment and Prognosis 303
23.7 D 2 Hydroxyglutaric Aciduria 303
23.7.1 Clinical Presentation 303
23.7.2 Metabolic Derangement 303
23.7.3 Genetics 303
23.7.4 Diagnostic Tests 304
23.7.5 Treatment and Prognosis 304
23.8 N Acetylaspartic Aciduria (Canavan Disease) . . . 304
23.8.1 Clinical Presentation 304
23.8.2 Metabolic Derangement 304
23.8.3 Genetics 304
23.8.4 Diagnostic Tests 304
23.8.5 Treatment and Prognosis 305
References 305
24 Nonketotic Hyperglycinemia
(Glycine Encephalopathy) 307
Olivier Dulac, Marie Odile Rolland
24.1 Clinical Presentation 309
24.1.1 Neonatal NKH 309
24.1.2 LateOnsetNKH 309
24.2 Metabolic Derangement 310
24.3 Genetics 311
24.4 Diagnostic Tests 311
24.5 Differential Diagnosis 311
24.6 Prenatal Diagnosis 312
24.7 Treatment 312
References 312
25 Disorders of Proline and Serine Metabolism 315
Jaak Jaeken
25.1 Inborn Errors of Proline Metabolism 317
25.1.1 Proline Oxidase Deficiency
(HyperprolinemiaTypel) 317
25.1.2 A' Pyrroline 5 Carboxylate Dehydrogenase
Deficiency (Hyperprolinemia Type II) 317
25.2 Inborn Errors of Serine Metabolism 318
25.2.1 3 Phosphoglycerate Dehydrogenase Deficiency 318
25.2.2 Phosphoserine Phosphatase Deficiency 318
25.2.3 Serine Deficiency with Ichthyosis and
Polyneuropathy 318
References 319
26 Transport Defects of Amino Acids at the
Cell Membrane: Cystinuria, Lysinuric
Protein Intolerance and Hartnup Disorder. . 321
Kirsti Nanto Salonen, Olli G. Simell
26.1 Cystinuria 323
26.1.1 Clinical Presentation 323
26.1.2 Metabolic Derangement 323
26.1.3 Genetics 323
26.1.4 Diagnostic Tests 323
26.1.5 Treatment and Prognosis 324
26.2 Lysinuric Protein Intolerance 324
26.2.1 Clinical Presentation 324
26.2.2 Metabolic Derangement 325
26.2.3 Genetics 325
26.2.4 DiagnosticTests 325
26.2.5 Treatment and Prognosis 326
26.3 Hartnup Disorder 326
26.3.1 Clinical Presentation 326
26.3.2 Metabolic Derangement 326
26.3.3 Genetics 327
26.3.4 DiagnosticTests 327
26.3.5 Treatment and Prognosis 327
References 327
V Vitamin Responsive Disorders
27 Biotin Responsive Disorders 331
Matthias R. Baumgartner, Terttu Suormala
27.1 Clinical Presentation 333
27.1.1 Holocarboxylase Synthetase Deficiency 333
27.1.2 Biotinidase Deficiency 333
27.1.3 Biotin Responsive Basal Ganglia Disease 334
27.2 Metabolic Derangement 334
27.3 Genetics 334
27.3.1 Holocarboxylase Synthetase Deficiency 334
27.3.2 Biotinidase Deficiency 335
27.3.3 Biotin Responsive Basal Ganglia Disease 335
27.4 DiagnosticTests 335
27.4.1 Holocarboxylase Synthetase Deficiency 335
27.4.2 Biotinidase Deficiency 336
27.4.3 Acquired Biotin Deficiency 336
27.4.4 Prenatal Diagnosis 336
27.5 Treatment and Prognosis 336
27.5.1 Holocarboxylase Synthetase Deficiency 336
27.5.2 Biotinidase Deficiency 336
27.5.3 Biotin Responsive Basal Ganglia Disease 337
References 337
28 Disorders of Cobalamin and Folate
Transport and Metabolism 341
David S. Rosenblatt, Brian Fowler
28.1 Disorders of Absorption and Transport
of Cobalamin 343
28.1.1 Hereditary Intrinsic Factor Deficiency 343
28.1.2 Defective Transport of Cobalamin by Enterocytes
(Imerslund Grasbeck Syndrome) 343
28.1.3 Haptocorrin (R Binder) Deficiency 344
28.1.4 Transcobalamin Deficiency 344
28.2 Disorders of Intracellular Utilization of Cobalamin 345
28.2.1 Combined Deficiencies of Adenosylcobalamin
and Methylcobalamin 345
28.2.2 Adenosylcobalamin Deficiency 347
28.2.3 Methylcobalamin Deficiency 348
28.3 Disorders of Absorption and Metabolism of Folate 351
28.3.1 Hereditary Folate Malabsorption 351
28.3.2 Glutamate Formiminotransferase Deficiency . 351
28.3.3 Methylenetetrahydrofolate Reductase
Deficiency 352
References 353
VI Neurotransmitter and
Small Peptide Disorders
29 Disorders of Neurotransmission 357
Jaak Jaeken, Cornelis Jakobs, Peter T. Clayton,
Ron A. Wevers
29.1 Inborn Errors of Gamma Amino Butyric
Acid Metabolism 361
29.1.1 Gamma Amino Butyric AcidTransaminase
Deficiency 361
29.1.2 Succinic Semialdehyde Dehydrogenase
Deficiency 362
29.2 Inborn Defects of Receptors and Transporters
ofNeurotransmitters 362
29.2.1 Hyperekplexia 362
29.2.2 GABA Receptor Mutation 363
29.2.3 Mitochondrial Glutamate Transport Defect. 363
29.3 Inborn Errors of Monoamine Metabolism 365
29.3.1 Tyrosine Hydroxylase Deficiency 365
29.3.2 Aromatic L Aminoacid Decarboxylase Deficiency 365
29.3.3 Dopamine (5 Hydroxylase Deficiency 366
29.3.4 Monoamine Oxidase A Deficiency 366
29.3.5 GuanosineTriphosphate Cyclohydrolase I
Deficiency 367
29.4 Inborn Disorders Involving Pyridoxine
and Pyridoxal Phosphate 369
29.4.1 Pyridoxine Responsive Epilepsy 369
29.4.2 Pyridox(am)ine 5' Phosphate Oxidase
Deficiency 370
References 371
30 Disorders in the Metabolism of Glutathione
and Imidazole Oipeptides 373
Ellinor Ristoff, Agne Larsson, Jaak Jaeken
30.1 Disorders in the Metabolism of Glutathione . . . 375
30.1.1 v Glutamylcysteine Synthetase Deficiency . 375
30.1.2 Glutathione Synthetase Deficiency 375
30.1.3 Y GlutamylTranspeptidase Deficiency 377
30.1.4 5 Oxoprolinase Deficiency 377
30.1.5 Secondary 5 Oxoprolinuria 377
30.2 Disorders of Imidazole Dipeptides 378
30.2.1 Serum Carnosinase Deficiency 378
30.2.2 Homocarnosinosis 378
30.2.3 Prolidase Deficiency 378
References 379
31 Trimethylaminuria and Dimethylglycine
Dehydrogenase Deficiency 381
Valerie Walker, Ron A. Wevers
31.1 Trimethylaminuria (Fish Odour Syndrome) . 383
31.1.1 Clinical Presentation 383
31.1.2 Metabolic Derangement 383
31.1.3 Genetics 383
31.1.4 Diagnostic Tests 383
31.1.5 Treatment 383
31.2 Dimethylglycine Dehydrogenase Deficiency . 384
31.2.1 Clinical Presentation 384
31.2.2 Metabolic Derangement 384
31.2.3 Genetics 384
31.2.4 Diagnostic Tests 384
31.2.5 Treatment 384
References 384
VII Disorders of Lipid and
Bile Acid Metabolism
32 Dyslipidemias 389
Annabelle Rodriguez Oquendo, Peter O. Kwiterovich, Jr.
32.1 Overview of Plasma Lipid and Lipoprotein
Metabolism 391
32.1.1 Exogenous Lipoprotein Metabolism 391
32.1.2 Endogenous Lipoprotein Metabolism 392
32.1.3 Reverse Cholesterol Transport and High Density
Lipoproteins 393
32.1.4 Lipid Lowering Drugs 394
32.2 Disorders of Exogenous Lipoprotein
Metabolism 394
32.2.1 Lipoprotein Lipase Deficiency 394
32.2.2 Apo C ll Deficiency 395
32.3 Disorders of Endogenous Lipoprotein
Metabolism 395
32.3.1 Disorders of VLDL Overproduction 396
32.3.2 Disorders of LDL Removal 397
32.4 Disorders of Endogenous and Exogenous
Lipoprotein Transport 399
32.4.1 Dysbetalipoproteinemia (Type III Hyperlipo
proteinemia) 399
32.4.2 Hepatic Lipase Deficiency 400
32.5 Disorders of Reduced LDL Cholesterol Levels . 400
32.5.1 Abetalipoproteinemia 400
32.5.2 Hypobetalipoproteinemia 401
32.5.3 Homozygous Hypobetalipoproteinemia 401
32.6 Disorders of Reverse Cholesterol Transport . 401
32.6.1 Familial Hypoalphalipoproteinemia 401
32.6.2 Apolipoprotein A l Mutations 401
32.6.3 Tangier Disease 402
32.6.4 Lecithin Cholesterol Acyltransferase Deficiency 402
32.6.5 Cholesteryl Ester Transfer Protein Deficiency . 402
32.6.6 Elevated Lipoprotein (a) 403
32.7 Guidelines for the Clinical Evaluation
and Treatment of Dyslipidemia 403
32.7.1 Clinical Evaluation 403
32.7.2 Dietary Treatment, Weight Reduction
and Exercise 404
32.7.3 Goals for Dietary and Hygienic Therapy 405
32.7.4 Low Density Lipoprotein Lowering Drugs . 406
32.7.5 Triglyceride Lowering Drugs 407
32.7.6 Combination Pharmacotherapy 408
Abbreviations 408
References 408
33 Disorders of Cholesterol Synthesis 411
Hans R. Waterham, Peter T. Clayton
33.1 Mevalonic Aciduria and Hyper lmmuno
globulinaemia D and Periodic Fever Syndrome
(Mevalonate Kinase Deficiency) 413
33.2 Smith Lemli Opitz Syndrome (7 Dehydro
cholesterol Reductase Deficiency) 414
33.3 X Linked Dominant Chondrodysplasia
Punctata 2 orConradi Hunermann Syndrome
(Sterol A8 A7 Isomerase Deficiency) 415
33.4 CHILD Syndrome (3(3 Hydroxysteroid
C 4 Dehydrogenase Deficiency) 416
33.5 Desmosterolosis (Desmosterol Reductase
Deficiency) 417
33.6 Lathosterolosis (Sterol A5 Desaturase Deficiency) 417
33.7 Hydrops Ectopic Calcification Moth Eaten
(HEM) Skeletal Dysplasia or Greenberg Skeletal
Dysplasia(SterolA14 ReductaseDeficiency) . 418
33.8 Other Disorders 419
References 419
34 Disorders of Bile Acid Synthesis 421
Peter T. Clayton
34.1 Introduction 423
34.2 3p Hydroxy A5 C27 Steroid Dehydrogenase
Deficiency 423
34.3 A4 3 Oxosteroid 5p Reductase Deficiency 425
34.4 Cerebrotendinous Xanthomatosis
(Sterol 27 Hydroxylase Deficiency) 426
34.5 a Methylacyl CoA Racemase Deficiency 427
34.6 Oxysterol 7a Hydroxylase Deficiency 428
34.7 Bile Acid Amidation Defect 428
34.8 Cholesterol 7a Hydroxylase Deficiency 429
34.9 Disorders of Peroxisome Biogenesis and
Peroxisomal (5 Oxidation 429
References 429
VIII Disorders of Nucleic Acid
and Heme Metabolism
35 Disorders of Purine and Pyrimidine
Metabolism 433
Georges van den Berghe, M. Francoise Vincent,
Sandrine Marie
35.1 Inborn Errors of Purine Metabolism 435
35.1.1 Phosphoribosyl Pyrophosphate Synthetase
Superactivity 435
35.1.2 Adenylosuccinase Deficiency 436
35.1.3 AICA Ribosiduria 437
35.1.4 Muscle AMP Deaminase Deficiency 437
35.1.5 Adenosine Deaminase Deficiency 438
35.1.6 Adenosine Deaminase Superactivity 439
35.1.7 Purine Nucleoside Phosphorylase Deficiency . 440
35.1.8 Xanthine Oxidase Deficiency 440
35.1.9 Hypoxanthine Guanine Phosphoribosyl
transferase Deficiency 441
35.1.10 Adenine Phosphoribosyltransferase Deficiency 442
35.1.11 Deoxyguanosine Kinase Deficiency 442
35.2 Inborn Errors of Pyrimidine Metabolism 445
35.2.1 UMP Synthase Deficiency (Hereditary Orotic
Aciduria) 445
35.2.2 Dihydropyrimidine Dehydrogenase Deficiency 445
35.2.3 Dihydropyrimidinase Deficiency 446
35.2.4 Ureidopropionase Deficiency 446
35.2.5 Pyrimidine 5' Nucleotidase Deficiency 446
35.2.6 Cytosolic 5' Nucleotidase Superactivity 447
35.2.7 Thymidine Phosphorylase Deficiency 447
35.2.8 Thymidine Kinase Deficiency 447
References 447
36 Disorders of Heme Biosynthesis 451
Norman G. Egger, Chul Lee, Karl E. Anderson
36.1 X Linked Sideroblastic Anemia 453
36.2 Classification of Porphyrias 453
36.3 Diagnosis of Porphyrias 454
36.4 5 Aminolevulinic Acid Dehydratase Porphyria 454
36.5 Acute Intermittent Porphyria 455
36.6 Congenital Erythropoietic Porphyria
(Gunther Disease) 458
36.7 PorphyriaCutaneaTarda 459
36.8 Hepatoerythropoietic Porphyria 460
36.9 Hereditary Coproporphyria and Variegate
Porphyria 461
36.10 Erythropoietic Protoporphyria 462
References 463
IX Disorders of Metal Transport
37 Disorders in the Transport of Copper, Zinc
and Magnesium 467
Roderick H.J. Houwen
37.1 Copper 469
37.1.1 Wilson Disease 469
37.1.2 Menkes Disease 471
37.1.3 Other Copper Storage Disorders 472
37.2 Zinc 472
37.2.1 Acrodermatitis Enteropathica 472
37.2.2 Zink Deficiency in Breastfed Babies 473
37.2.3 Hyperzincemia with Hypercalprotectinemia . . . 473
37.2.4 Autosomal Dominant Hyperzincemia Without
Symptoms 473
37.3 Magnesium 474
37.3.1 Primary Hypomagnesemia with Secondary
Hypocalcemia 474
37.3.2 Hypomagnesemia with Hypercalciuria and
Nephrocalcinosis 474
37.3.3 Isolated Dominant Hypomagnesemia 475
37.3.4 Isolated Autosomal Recessive Hypomagnesemia 475
37.3.5 OtherMetals 475
References 475
X Organelle Related Disorders:
Lysosomes, Peroxisomes, and
Golgi and Pre Golgi Systems
38 Disorders of Sphingolipid Metabolism . 479
Marie Therese Vanier
38.1 Gaucher Disease 481
38.2 Niemann PickDiseaseTypeAandB 482
38.3 GMI Gangliosidosis 484
38.4 GM2 Gangliosidoses 485
38.5 Krabbe Disease 486
38.6 Metachromatic Leukodystrophy 487
38.7 Fabry Disease 489
38.8 Farber Disease 490
38.9 Prosaposin Deficiency 490
38.10 Niemann Pick Disease Type C 491
References 492
39 Mucopolysaccharidoses and Oligo
saccharidoses 495
/. Ed Wraith
39.1 Clinical Presentation 497
39.1.1 Mucopolysaccharidoses 497
39.1.2 Oligosaccharidoses 505
39.2 Metabolic Derangements 506
39.3 Genetics 506
39.4 Diagnostic Tests 506
39.5 Treatment and Prognosis 506
References 507
40 Peroxisomal Disorders 509
Bwee Tien Poll The, Patrick Aubourg,
Ronald J.A. Wanders
40.1 Clinical Presentation 511
40.1.1 Dysmorphism 511
40.1.2 Neurological Dysfunction 512
40.1.3 Hepatic and Gastrointestinal Disease 512
40.2 Metabolic Derangements 514
40.2.1 Peroxisome Biogenesis 514
40.2.2 Metabolic Functions of Peroxisomes 515
40.2.3 Metabolic Abnormalities in the Different
Peroxisomal Disorders 518
40.3 Genetics 519
40.4 Diagnostic Tests 519
40.4.1 Diagnostic Group 1 519
40.4.2 Diagnostic Group 2 519
40.4.3 Diagnostic Group 3 519
40.4.4 Diagnostic Group 4 520
40.4.5 Histological Detection 520
40.4.6 Prenatal Diagnosis 520
40.5 Treatment and Prognosis 520
References 521
41 Congenital Disorders of Glycosylation . 523
Jaakjaeken
41.1 Introduction 525
41.2 Congenital Disorders of Protein N Glyco
sylation 526
41.2.1 Phosphomannomutase 2 Deficiency (CDG la) . . 526
41.2.2 Phosphomannose lsomerase Deficiency
(CDG lb) 527
41.2.3 Glucosyltransferase I Deficiency (CDG lc) 528
41.3 Congenital Disorders of Protein O Glyco
sylation 528
41.3.1 Hereditary Multiple Exostoses 528
41.3.2 Walker Warburg Syndrome 529
41.3.3 Muscle Eye Brain Disease 529
41.4 Newly Discovered Disorders 529
41.4.1 COG7 Deficiency 529
41.4.2 GM3 Synthase Deficiency 529
References 530
42 Cystinosis 531
Michel Broyer
42.1 Infantile Cystinosis 533
42.1.1 Clinical Presentation 533
42.1.2 Metabolic Derangement 534
42.1.3 Genetics 535
42.1.4 Diagnostic Tests 535
42.1.5 Treatment 535
42.2 Adolescent Cystinosis 536
42.3 Adult Benign Cystinosis 536
References 536
43 Primary Hyperoxalurias 539
Pierre Cochat, Marie Odile Rolland
43.1 Primary Hyperoxaluria Type 1 541
43.1.1 Clinical Presentation 541
43.1.2 Metabolic Derangement 542
43.1.3 Genetics 542
43.1.4 Diagnosis 542
43.1.5 Treatment and Prognosis 542
43.2 Primary Hyperoxaluria Type 2 545
43.2.1 Clinical Presentation 545
43.2.2 Metabolic Derangement 545
43.2.3 Genetics 545
43.2.4 Diagnosis 545
43.2.5 Treatment and Prognosis 545
43.3 Non Type 1 Non Type 2 Primary Hyperoxaluria . . 545
References 545
Subject Index 547 |
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| index_date | 2024-07-02T17:04:52Z |
| indexdate | 2025-02-20T07:02:45Z |
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| spellingShingle | Inborn metabolic diseases diagnosis and treatment ; with 63 tables Stoffwechselkrankheit (DE-588)4057700-4 gnd Angeborene Krankheit (DE-588)4331107-6 gnd |
| subject_GND | (DE-588)4057700-4 (DE-588)4331107-6 |
| title | Inborn metabolic diseases diagnosis and treatment ; with 63 tables |
| title_auth | Inborn metabolic diseases diagnosis and treatment ; with 63 tables |
| title_exact_search | Inborn metabolic diseases diagnosis and treatment ; with 63 tables |
| title_exact_search_txtP | Inborn metabolic diseases diagnosis and treatment ; with 63 tables |
| title_full | Inborn metabolic diseases diagnosis and treatment ; with 63 tables John Fernandes ... (eds.) |
| title_fullStr | Inborn metabolic diseases diagnosis and treatment ; with 63 tables John Fernandes ... (eds.) |
| title_full_unstemmed | Inborn metabolic diseases diagnosis and treatment ; with 63 tables John Fernandes ... (eds.) |
| title_short | Inborn metabolic diseases |
| title_sort | inborn metabolic diseases diagnosis and treatment with 63 tables |
| title_sub | diagnosis and treatment ; with 63 tables |
| topic | Stoffwechselkrankheit (DE-588)4057700-4 gnd Angeborene Krankheit (DE-588)4331107-6 gnd |
| topic_facet | Stoffwechselkrankheit Angeborene Krankheit |
| url | https://doi.org/10.1007/978-3-540-28785-8 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015574242&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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