دانلود کتاب Inherited Metabolic Diseases + Ereference A Clinical Approach

فهرست مطالب :

Preface......Page 8
General Introduction......Page 10
Contents......Page 12
Contributors......Page 16
Part I: Introduction to Inborn Errors of Metabolism......Page 19
1: Disorders of Intermediary Metabolism......Page 20
1.2 Organic Acidurias......Page 21
1.5 Disorders of Peptide Metabolism......Page 22
1.8 Mitochondrial Disorders......Page 23
1.10 Disorders of the Transport or Utilization of Copper, Manganese, Iron, and Zinc......Page 24
2.2 Lysosomal Storage Disorders......Page 26
2.3 Peroxisomal Disorders......Page 27
2.6 Disorders of Posttranslation Protein Modification......Page 28
2.7 Disorders of Lipoprotein Metabolism......Page 29
3.2 Disorders of the Metabolism of Pterins and Biogenic Amines......Page 30
3.5 Related Neurometabolic Disorders......Page 31
Part II: Approach to the Patient......Page 33
4.1.1 Family History......Page 34
4.1.3 Age of Presentation and Precipitating Factors......Page 35
4.2.1 Unusual Odor......Page 37
4.2.2.1 Examination of the Urine for the Significance of Color......Page 39
4.2.2.3 Red Urine......Page 40
4.4 When Not to Suspect a Metabolic Disease......Page 41
References......Page 43
5.1 General Aspects......Page 44
References......Page 45
6: Inherited Metabolic Diseases in the Context of Rare/Orphan Diseases......Page 46
References......Page 47
7.1 General Considerations......Page 48
7.1.2 Communication in the Field of Inherited Metabolic Diseases......Page 49
7.1.4 Use of Ambiguous and New Terms......Page 50
7.1.6 Nonverbal Communication......Page 51
7.1.8 Talking About Numbers......Page 52
7.1.11 Overestimation of Competence......Page 53
References......Page 54
8.1 Guidelines......Page 56
8.2 Follow-Up......Page 57
References......Page 58
9.1 What Can a Patient or Family Affected by an Inherited Metabolic Disease Expect from a Support Organisation......Page 59
9.2 Further Information......Page 60
10.1 Transition of Healthy Adolescents and Young Adults......Page 62
10.2 Transition of Adolescents with Chronic Diseases......Page 63
10.2.3 Health-Care Settings......Page 64
10.3 Results of Pediatric Transition Programs for Specific Diseases......Page 65
10.5 Transition Within the National Health-­Care Systems......Page 67
10.6.2.1 Medical Knowledge......Page 69
10.6.2.2 Adult Health-Care System Expectations......Page 70
10.6.3 Possible Solutions......Page 71
References......Page 72
11.2 The Preconception Period......Page 74
11.3 Fertility and Miscarriage......Page 76
11.4 Teratogenicity......Page 78
11.5.1 Dietary Restrictions......Page 81
11.5.4 Learning Disability......Page 85
11.5.6 Association of Foetal FAOD and Maternal Illness in Pregnancy......Page 86
11.8 Postpartum......Page 88
References......Page 90
12: Metabolic Emergencies......Page 94
12.1 Neonates......Page 99
12.2 Infancy......Page 101
12.3 Older Children and Adults......Page 103
13: Workup of the Patient with Metabolic Acidosis and Massive Ketosis......Page 104
References......Page 107
14: Workup of the Patient with Lactic Acidemia: Mitochondrial Disease......Page 108
14.1 Workup of a Patient with Lactic Acidemia (Congenital)......Page 110
References......Page 112
15: Work-Up of the Patient with Hypoglycemia......Page 113
15.1 Algorithmic Approach to Diagnosis......Page 114
15.3 Disorders of Carbohydrate Metabolism......Page 117
References......Page 118
16: Approach to the Child Suspected of Having a Disorder of Fatty Acid Oxidation......Page 119
References......Page 123
17: Work-Up of the Patient with Hyperammonemia......Page 124
General Suggestions for Reading......Page 128
18: Work-Up of the Patient with Acute Neurological or Psychiatric Manifestations......Page 129
General Suggestions for Reading......Page 134
19: Emergency Treatment of Inherited Metabolic Diseases......Page 135
19.1 Acute Intoxication (Fig. 4.1)......Page 136
19.2 Reduced Fasting Tolerance (Fig. 4.1)......Page 139
19.3 Disturbed Energy Metabolism (Fig. 4.1)......Page 140
General Suggestions for Reading......Page 141
20: Anesthesia and Metabolic Disease......Page 142
20.3 Avoidance of Hypoglycemia......Page 143
20.5 Organic Acidemias and Maple Syrup Urine Disease......Page 144
20.7 Mitochondrial Disease......Page 145
References......Page 146
21.2 Core Elements of Dietary Treatment......Page 147
21.2.2 Acute Dietary Management......Page 148
21.2.3 Nutritional Support and Feeding Problems......Page 149
21.2.5 Monitoring of Biochemical Control......Page 150
21.3.1 Disorders of Amino Acid Metabolism......Page 151
21.3.2.2 IVA (Affecting Leucine Catabolism)......Page 154
21.3.3 Disorders of Urea Cycle Disorders......Page 155
21.3.4.1 Galactosaemia......Page 156
21.3.4.2 Hereditary Fructosaemia (HFI)......Page 157
21.3.4.5 GSD Type Ib......Page 158
21.3.5.3 MCT......Page 159
21.3.5.9 MCADD (Medium Acyl-CoA Dehydrogenase Deficiency)......Page 160
References......Page 161
22.1 Introduction......Page 162
22.2.1 Fundamentals......Page 163
22.2.2 Available Methods for Gene Transfer......Page 165
22.2.3 Gene Editing......Page 167
22.3.1 Bone Marrow-Directed Gene and Cell Therapy for IEM......Page 168
22.3.2.1 Therapeutic Liver Repopulation Through Hepatocyte Transplantation......Page 171
22.3.2.2 Liver-Directed Gene Therapy......Page 172
Conclusion......Page 175
References......Page 176
Part III: Organ Systems in Metabolic Disease......Page 179
23.1 General Remarks......Page 180
23.2.1 Special Aspects of Cardiac Metabolism......Page 181
23.2.2 Patterns and Pathophysiology of Metabolic Cardiac Disease......Page 187
23.2.3.1 Disorders of Fatty Acid Oxidation and the Carnitine Cycle......Page 188
23.2.3.2 Mitochondrial Disorders......Page 191
23.2.3.3 Disorders of Amino and Organic Acid Metabolism......Page 193
23.2.3.4 Lysosomal Storage Disorders (Infiltrative Cardiomyopathies)......Page 194
23.2.3.6 Disorders of Glycoprotein Metabolism......Page 195
Selenium......Page 196
23.2.4 Investigations for Metabolic Cardiomyopathies......Page 197
23.2.5 Principles of Treatment in Metabolic Cardiomyopathy......Page 198
23.3 Dysrhythmias and Conduction Disturbances......Page 201
23.5 Thromboembolic and Vascular Disorders......Page 202
23.6 Pulmonary Hypertension......Page 203
Key References......Page 206
24: Liver Disease......Page 207
24.1 General Remarks......Page 208
24.2.1 Cholestatic Liver Disease in Early Infancy......Page 209
24.2.2 Cholestatic Liver Disease in Later Infancy and Childhood......Page 212
24.3.1 Fulminant Liver Failure in Early Infancy......Page 213
24.3.2 Hepatic Failure in Later Infancy and Childhood......Page 216
24.4 Cirrhosis......Page 222
24.5 Hepatomegaly......Page 224
24.5.1 The Glycogenoses......Page 227
References......Page 229
25.2 Vomiting......Page 231
25.3 Abdominal Pain......Page 232
25.3.1 The Porphyrias......Page 233
25.4 Pancreatitis......Page 234
25.7 Diarrhea......Page 235
25.8.1 Disaccharide Intolerance I: Sucrase/Isomaltase Deficiency......Page 236
25.9 Malabsorption......Page 237
25.9.4 Amino Acids......Page 238
25.9.5.1 Vitamin B12......Page 239
References......Page 240
26.1 General Remarks......Page 242
26.2 Dehydration......Page 243
26.3 Urinary Tract Calculi......Page 244
26.4 Renal Tubular Dysfunction Fanconi Syndrome......Page 247
26.4.1 Cystinosis......Page 248
26.4.2 Renal Tubular Acidosis......Page 249
26.4.3 Bartter Syndrome......Page 250
26.4.4 Gitelman Syndrome......Page 251
26.5 Investigation for Renal Tubular Dysfunction......Page 252
General Suggestions for Reading......Page 253
27: Neurological Disease......Page 254
27.2 History and Neurological Examination......Page 255
27.3 Neurological Regression/Deterioration......Page 256
27.4 Global Developmental Delay/Mental Retardation......Page 260
27.5 Delayed Speech Development......Page 262
27.6 Deafness......Page 263
27.7.1 Neonatal Period......Page 266
27.7.3 Infancy......Page 269
27.7.4 Childhood and Adolescence......Page 272
27.9.1 Ataxia......Page 274
27.9.1.3 Progressive Ataxia......Page 276
27.9.1.4 Vitamin E-Responsive Ataxias (AVED, Ataxias with Isolated Vitamin E Deficiency)......Page 277
27.9.2 Dystonia, Parkinsonism, and Chorea......Page 278
27.9.3 Dystonia......Page 279
27.9.5 Chorea......Page 285
27.9.6 Spasticity......Page 286
27.9.6.1 Treatable Inborn Errors of Metabolism with Prominent Di/Tetraparesis......Page 288
27.9.6.2 Progressive Spasticity Associated with Multiple Neurologic Signs, Irritability, and Global Deterioration......Page 289
27.10 Neurophysiology......Page 290
27.11 Diagnostic Lumbar Puncture......Page 291
References......Page 293
28.1 General Remarks......Page 296
28.1.2 Basic Patterns of Metabolic Myopathies......Page 301
28.2 Approach to Metabolic Myopathies......Page 303
28.2.3 Laboratory Investigations......Page 304
Muscle Glycogen Phosphorylase (Myophosphorylase) Deficiency: McArdle Disease (GSD Type V)......Page 305
Adenosine Monophosphate (Myoadenylate) Deaminase Deficiency......Page 306
CPT II Deficiency......Page 308
LCHAD (Including Trifunctional Protein) Deficiency......Page 309
28.3.2.1 Carnitine Transporter Deficiency......Page 310
28.3.2.4 MADD–ETF OR ETF-­Dehydrogenase Deficiency (Synonymously Glutaric Aciduria Type II)......Page 311
28.3.2.6 Glycogen Debrancher Deficiency: GSD Type III (Cori or Forbes Disease)......Page 312
28.3.2.9 Mitochondrial Myopathies and Coenzyme Q Deficiency......Page 313
28.3.4 Malignant Hyperthermia......Page 314
References......Page 315
29.1 General Remarks......Page 316
29.2 Acute Psychiatric Manifestations......Page 317
29.3.3 Childhood and Early Adolescence (5–15 Years)......Page 318
29.3.4 Late Adolescence and Adulthood (>15 Years)......Page 319
References......Page 320
30.1 General Remarks......Page 321
30.3 Corneal Clouding......Page 322
Lysosomal Disorders......Page 323
30.4.1 Cataracts......Page 327
Lipid Metabolism Disorders......Page 329
Congenital Disorders of Glycosylation......Page 330
30.4.2 Ectopia Lentis (Lens Dislocations)......Page 331
30.5 Degeneration of the Choroid and the Retina......Page 332
Gyrate Atrophy of the Choroid and Retina (GACR) and Retinitis Pigmentosa (RP)......Page 333
30.5.1 Pigment Retinopathies......Page 335
30.6 Optic Atrophy......Page 337
Mitochondrial Disorders......Page 338
Peroxisomal Disorders......Page 339
30.6.3 Other Secondary Metabolic Optic Atrophies......Page 340
References......Page 341
31.1 General Remarks......Page 342
31.2.2 Acrocyanosis, Angiomas, and Telangiectasia......Page 344
31.3 Skin Eruptions (Table 31.2)......Page 346
31.4 Ichthyosis (Table 31.3)......Page 350
31.5 Papular and Nodular Skin Lesions (Table 31.4)......Page 355
31.6.1 Hypopigmentation......Page 359
31.6.2 Hyperpigmentation......Page 361
31.7 Photosensitivity (Table 31.6)......Page 362
31.8.1 Hair Shaft Abnormalities......Page 364
31.8.2 Hypertrichosis (Table 31.8)......Page 365
31.9 Skin Laxity (Table 31.9)......Page 367
31.10 Other Lesions (Table 31.10)......Page 370
References......Page 371
32: The Bone in Genetic and Metabolic Diseases: A Practical Approach......Page 372
32.2 What Skeletal Radiographs Are Needed?......Page 375
32.4 Therapeutic Implications......Page 380
References......Page 381
33.2 Definitions......Page 382
33.3 Lysosomal Storage Disorders: Disturbed Degradation of Macromolecules in Lysosomes......Page 383
33.4 Peroxisomal Disorders: Disturbance of Biogenesis or of Modification of Substrates......Page 390
33.6 Disorders of Cholesterol Biosynthesis: Disorders Affecting Developmental Signalling Pathways......Page 392
33.7 Energy Defects: Mitochondrial Defects Potentially Affecting Morphogenesis......Page 394
33.8 Disorders of Post-­translational Protein Modification: Congenital Disorders of Glycosylation and GPI Anchor Disorders......Page 395
References......Page 399
34: Hematological Disorders......Page 401
34.3 Hemolytic Anemia......Page 402
34.4 Macrocytic Anemia......Page 406
34.5 Sideroblastic Anemia......Page 407
34.10 Hemophagocytosis......Page 408
General Suggestions for Reading......Page 410
35: Immunological Problems......Page 411
35.2 Inherited Metabolic Diseases Associated with T Cell Immunodeficiency......Page 412
35.3 Inherited Metabolic Diseases Associated with B Cell Immunodeficiency......Page 413
35.4 Inherited Metabolic Diseases Associated with Combined T and B Cell Immunodeficiency......Page 414
35.5 Inherited Metabolic Diseases Associated with Phagocyte Immunodeficiency......Page 416
35.6 Inherited Metabolic Diseases Associated with NK Cell Immunodeficiency......Page 417
References......Page 418
Part IV: Investigations for Metabolic Diseases......Page 419
36: Newborn Screening for Inherited Metabolic Disease......Page 420
36.1 Hyperphenylalaninemias and Other Inborn Errors of Amino Acid Metabolism......Page 428
36.2 Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency and Other Inborn Errors of Mitochondrial Fatty Acid Metabolism......Page 429
36.3 Biotinidase Deficiency and Other Inborn Errors of Organic Acid Metabolism......Page 430
36.4 Galactosemia......Page 431
36.5 Congenital Hypothyroidism......Page 432
36.6 Congenital Adrenal Hyperplasia (CAH)......Page 433
36.7.3 Lysosomal Storage Disorders (LSD)......Page 434
36.7.5 Sickle Cell Disease and Other Hemoglobinopathies, Congenital Infections, Hearing Loss, and Critical Congenital Heart Disease......Page 435
References......Page 436
37.1 General Remarks......Page 437
37.4 Reducing Substances in Urine......Page 439
37.7 Ehrlich’s Aldehyde Reagent......Page 440
37.9 Sulfite Test......Page 441
37.10.1 Plasma......Page 442
37.10.2 Urine......Page 443
37.11 Organic Acids......Page 444
37.13 Carnitine Status......Page 446
37.14 Lactate, Pyruvate, Ketone Bodies, and Nonesterified Fatty Acids......Page 447
37.15 Investigations for Congenital Disorders of Glycosylation (CDG)......Page 448
37.16 Purines and Pyrimidines......Page 449
37.18 Disorders of Galactose Metabolism......Page 450
37.21 Glutathione (and Analogues)......Page 451
37.23 Oligosaccharides......Page 452
37.24 Peroxisomal Function: Very Long-Chain Fatty, Phytanic, and Pristanic Acids......Page 453
37.26 Folate Metabolites......Page 454
37.28 Bile Acids......Page 455
37.30 Biogenic Amines and Pterins (Specialized CSF/Urine Analyses)......Page 456
References......Page 458
38: Enzyme Diagnostics in a Changing World of Exome Sequencing and Newborn Screening as Exemplified for Peroxisomal, Mitochondrial, and Lysosomal Disorders......Page 459
38.1 Introduction......Page 460
38.2 Basic Principles of Enzymes and Enzyme Diagnostics Relevant for IEMs......Page 462
38.3 Enzyme Diagnostics......Page 464
38.5.1.1 Background......Page 465
38.5.1.3 Enzymology of the Peroxisomal Disorders......Page 467
38.5.2.3 Enzymatic Analysis of FAO Disorders......Page 469
38.5.3.1 Background......Page 471
38.5.3.2 Laboratory Diagnosis of Mitochondrial Disorders......Page 472
38.5.4.1 Biochemical Background......Page 474
Single Enzyme Deficiencies (See Tables 38.3 and 38.4)......Page 475
Multiple Enzyme Deficiencies (See Table 38.5)......Page 478
Lysosomal/Endosomal Trafficking Defects (See Table 38.6)......Page 479
Metabolite Analysis......Page 480
Lysosomal/Endosomal Trafficking Defects (See Table 38.6)......Page 481
38.5.4.5 Mutation Analysis......Page 482
References......Page 483
39: Molecular Genetic Analyses......Page 486
39.1 From Genotype to Phenotype......Page 487
39.2 Indications for a Molecular Genetic Analysis......Page 488
39.3.1 Testing for Common Mutations......Page 489
39.3.3 Massively Parallel (“Next-­Generation”) Sequencing......Page 490
39.3.4 Autozygosity Mapping......Page 492
39.4 Samples......Page 493
39.5 Pitfalls......Page 494
References......Page 495
40.1 General Remarks......Page 496
40.2 Carrier Tests......Page 497
40.3 Prenatal Diagnosis......Page 498
40.4 Preimplantation Genetic Diagnosis and Polar Body Analysis......Page 499
References......Page 500
41: Function Tests......Page 501
41.2.1 Monitored Prolonged Fast......Page 502
41.2.1.2 Procedure......Page 504
41.2.1.3 Treatment of Adverse Reactions......Page 505
41.2.1.4 Interpretation......Page 506
41.2.2 Preprandial/Postprandial Analyses (Protein/Glucose Challenge)......Page 509
41.2.3 Glucose Challenge......Page 510
41.2.4 Glucagon Stimulation......Page 511
41.3.1.2 Interpretation......Page 512
41.3.2.1 Procedure......Page 513
41.3.3 Vitamin B12 Test......Page 514
41.3.4.1 Procedure and Interpretation......Page 515
References......Page 516
42.1 Background......Page 517
42.2 Mitochondrial Genetics......Page 518
42.3 Clinical Recognition of Mitochondrial Disease......Page 519
42.4 General Approach to a Patient with Suspected Mitochondrial Disorder......Page 525
42.5 Neuroimaging......Page 527
42.7 Muscle Biopsy......Page 528
42.8 Genetic Investigations......Page 529
42.10 Differential Diagnosis......Page 530
References......Page 531
43.1 General Remarks......Page 532
43.2 Circulating Blood Cells......Page 534
43.3 Skin......Page 536
43.5 Peripheral Nervous System......Page 539
43.6 Rectum......Page 540
43.8 Liver......Page 541
43.9 Skeletal Muscle......Page 542
References......Page 545
44: Postmortem Investigations......Page 546
44.1.3 Urine......Page 548
References......Page 549
45.1.1 T2-Weighted and FLAIR Images......Page 550
45.4 Pattern Recognition Approach in Interpreting MRI......Page 551
45.5 Diffusion-Weighted Imaging......Page 553
45.6 1H-MR Spectroscopy......Page 554
45.7 Major Metabolites......Page 555
45.9 Suggested Standard MRI Protocol......Page 557
45.10.2.1 Generalised Atrophy......Page 558
45.10.2.3 Cortical Involvement......Page 560
45.10.3.2 Organic Acidurias and Mitochondrial Disorders......Page 562
45.10.3.3 Disorders of Amino Acid Metabolism......Page 563
References......Page 564
Differential Diagnosis of Clinical and Biochemical Phenotypes......Page 566
Reference Books......Page 579
Internet Resources......Page 580
Index......Page 582