Lysosomal Storage Disorders: Principles And Practice Principles and Practice

This book presents an overview of lysosomal storage disorders, and provides the reader with an understanding of clinical features, associated complications, and diagnosis and management approaches. It also describes historical developments in the field and current thinking relating to pathophysiology and prospective therapeutic strategies. The book is written by an expert in the field who has been engaged in both basic and clinical research, in addition to having extensive practical experience in patient care. It is written from the perspective of someone who entered the field just as treatment was being introduced, and who has been engaged in the seminal clinical trials and the development of therapeutic guidelines. It offers a broad perspective and should appeal to both novices and experts in the field who seek a single resource that provides a comprehensive picture of relevant topics on this subject. A multi-faceted volume, the author addresses the issue of diagnosis and patient management, underlying mechanisms of disease, sources of morbidity and treatment options, covering issues of interest to both the basic scientist and the clinician. Foreword......Page 6 Preface......Page 8 Contents......Page 12 List of Abbreviations......Page 14 List of Figures......Page 18 Vignette......Page 20 The Lysosome and Storage Defects......Page 24 Clinical Presentations and Diagnosis......Page 31 Screening and Genetic Counseling Issues......Page 37 References......Page 38 Vignette......Page 40 2. Clinical Perspectives......Page 42 Manifesting Signs and Corresponding Diagnostic Entities......Page 43 Generalized: Non-immune hydrops fetalis......Page 44 Head, eyes, nose, ears and throat involvement......Page 50 Neurologic problems (Table 2.2)......Page 54 Cardiopulmonary problems......Page 56 Visceral problems......Page 57 Skeletal problems......Page 58 References......Page 59 Vignette......Page 62 3. Diagnostic Confirmation and Screening Protocols......Page 66 Points of note......Page 70 Diagnostic confirmation, including prenatal diagnosis......Page 68 Biochemical Testing......Page 69 Molecular Testing......Page 71 Specialized Testing and Other Considerations......Page 73 Screening Programs......Page 74 Issues Related to Genetic Counseling......Page 76 References......Page 77 Vignette......Page 82 4. Assessment of Disease Burden and Assignment of Disease Severity......Page 84 Nervous system involvement......Page 85 Cardiopulmonary involvement......Page 89 Musculoskeletal involvement......Page 90 Disease Severity Scores......Page 91 Quality of Life Studies......Page 107 References......Page 110 Vignette......Page 116 5. Pathophysiology and Biomarkers......Page 118 Morphological Observations and Biochemical Correlates......Page 120 1. Neurotoxicity and aberrant inflammation......Page 125 2. Activation of ER-stress response, oxidative stress and apoptosis......Page 128 3. Autophagy and associated defects......Page 129 Miscellaneous Findings......Page 130 Biomarkers and Their Roles in Assignment of Disease Activity or Severity, and Changes in Patient Profile in Response to Therapy......Page 132 References......Page 135 Vignette......Page 142 6. Current and Emerging Therapies......Page 144 Cellular Transplantation......Page 145 Biochemical and Molecular Observations......Page 124 Enzyme Replacement Therapy (ERT)......Page 147 Substrate Reduction Therapy (SRT)......Page 149 Substrate Depletion or Modulation Therapy......Page 150 Chaperone-Mediated Enzyme Enhancement Therapy......Page 151 Gene Therapy......Page 152 Palliative Care......Page 153 Organ Transplantation......Page 154 Further Points to Consider......Page 155 References......Page 156 Lysosomal Biogenesis and Function......Page 162 Pathogenesis......Page 163 Animal Models......Page 164 Phenotype......Page 165 Blood-Brain Barrier......Page 166 Strategies to Improve Therapeutic Outcome......Page 167 References......Page 168 Disease Index......Page 172 General Index......Page 176 "This book presents an overview of lysosomal storage disorders, and provides the reader with an understanding of clinical features, associated complications, and diagnostic and management approaches. It also describes historical developments in the field and current thinking relating to pathophysiology and prospective therapeutic strategies." "The book is written by an expert in the field who has been engaged in both basic and clinical research, in addition to having extensive practical experience in patient care. It is written from the perspective of someone who entered the field just as treatment was being introduced, and who has been engaged in the seminal clinical trials and the development of therapeutic guidelines. It offers a broad perspective and should appeal to both novices and experts in the field who seek a single resource that provides a comprehensive picture of relevant topics on this subject." --Book Jacket 1. Introduction -- 2. Clinical perspectives -- 3. Diagnostic confirmation and screening protocols -- 4. Assessment of disease burden and assignment of disease severity -- 5. Pathophysiology and biomarkers -- 6. Current and emerging therapies -- 7. Future prospects