Lysosomal Storage Disorders

Awareness of lysomal storage disorders needs to be raised and there is very substantial pharmaceutical interest to do so. The disorders are often viewed as obscurities but in fact they are treatable. Enzyme replacement therapy is available for four of the disorders and will be available for a further three disorders in the course of the next year. Substrate reduction therapy is licensed for one of them but in the course of the next 12 months it will be licensed for two others and a new form of substrate reduction therapy is being introduced. These diseases present to a very wide range of physicians and paediatricians. Gaucher disease may present to orthopaedic surgeons or haematologists with splenomegaly and/or skeletal disease. However, paediatricians see the childhood variants of Gaucher disease and therefore may present it to neurologists. Fabry disease typically does not present in childhood but presents to adult physicians with end organ damage (renal failrure, cardiac disease, stroke, neuropathy, gastrointestinal symptoms). A text book would draw these divergent strands together. There is substantial scientific interest in these diseases. Gaucher is well recognised as a paradigm of a molecular illness, understood at a basic level which is treatable now with specific therapy and is likely to be treatable with gene therapy within the coming five years. New advances in small molecule therapy – e.g. chaperone treatment, modified antibiotics affecting ribosomal function – are likely to be useful for these diseases in the near future. Trials are already underway. These diseases therefore offer a fabulous platform for teaching modern clinical science from basic genetics right the way through to clinical applications. CONTENTS Part 1: General Aspects of Lysosomal Storage Diseases 1 The Lysosomal System: Physiology and Pathology Matthew C. Micsenyi, Steven U. Walkley 2 Clinical Aspects and Clinical Diagnosis Ed Wraith, Michael Beck 3 Laboratory Diagnosis of LSDs Bryan Winchester 4 Genetics of Lysosomal Storage Disorders and Counseling John J. Hopwood 5 Integrated Classification Bryan Winchester Part 2: The Individual Diseases 6 Gaucher Disease Deborah Elstein, Ari Zimran 7 Fabry Disease Atul Mehta, Uma Ramaswami 8 The Gangliosidoses Joe T.R. Clarke 9 Metachromatic Leukodystrophy and Globoid Cell Leukodystrophy Volkmar Gieselmann, David A. Wenger, Ingeborg Krägeloh-Mann 10 Types A and B Niemann-Pick Disease Melissa P. Wasserstein, Robert J. Desnick, Edward H. Schuchman 11 Niemann-Pick Disease Type C Marie T. Vanier, Marc C. Patterson 12 The Mucopolysaccharidoses Roberto Giugliani 13 Pompe Disease Arnold J. J. Reuser, Ans T. van der Ploeg 14 Glycoproteinoses Dag Malm, Hilde Monica F. Riise Stensland, Øivind Nilssen 15 Multiple Enzyme Deficiencies: Defect in Protective Protein/Cathepsin A: Galactosialidosis Alessandra d’Azzo, Erik J. Bonten 16(i) Multiple Enzyme Deficiencies: Defects in transport: Mucolipidosis II alpha/beta; mucolipidosis III alpha/beta and mucolipidosis III gamma Annick Raas-Rothschild, Sandra Pohl, Thomas Braulke 16(ii) Multiple Enzyme Deficiencies: Multiple Sulfatase Deficiency Andrea Ballabio, Graciana Diez-Roux 17 Lysosomal Membrane Defects Michael Schwake, Paul Saftig 18 Neuronal Ceroid Lipofuscinoses Jonathan D. Cooper, Ruth E. Williams 19 Other Lysosomal Diseases Atul Mehta, Bryan Winchester Part 3: Therapy and Patient Issues 19 Current Treatments Timothy M. Cox 20 Central Nervous System Aspects, Neurodegeneration and the Blood-Brain Barrier David J. Begley, Maurizo Scarpa 21 Emerging Treatments / Future Outcome T. Andrew Burrow, Gregory A. Grabowski 22 Newborn, High Risk and Carrier Screening for LSDs Gabor E. Linthorst, Carla E.M. Hollak 23 The Patient Perspective on Rare Diseases Alastair Kent, Christine Lavery, Jeremy Manuel