Table Of ContentLysosomal Storage Disorders
Lysosomal Storage Disorders
Jo hn A. Barranger, M.D., Ph.D.
Mario A. Cabrera-Salazar, M.D.
John A. Barranger, MD, PhD Mario A. Cabrera-Salazar, MD
Department of Human Genetics Genzyme Corporation
University of Pittsburgh Framingham, MA 01701–9322
Pittsburgh, PA 15261 USA
USA
To all those colleagues and friends
who made this text as good
as it is, I remain in debt.
Thank you for your thoughtful contributions.
John A. Barranger
To my parents Jorge and Sonia
and Luis Antonio, my grandfather;
a teacher who mastered the science
of educating generations.
Mario A. Cabrera-Salazar
To all patients with lysosomal storage
disorders, thank you for all the lessons
given to us
Preface
Scientific progress has been rapid in lysosomal biology during the last six decades. Its
application to human disease is nothing less than spectacular. In no other group of
disorders has knowledge and clinical utility progressed so speedily. Recall that the
organelle was described in just 1955. Since then, the biochemical alterations and storage
materials were described, the enzyme deficiencies discovered, the gene coding of
these glycoproteins cloned and thousands of mutations defined. These advances have
resulted in highly improved diagnosis for more than 50 diseases. For five diseases,
including the most common lysosomal storage disorder, molecular therapy is a reality,
extremely effective and very safe. This higher plateau of medical approaches to human
disease is something to which all translational scientists aspire and only a few actually
witness. The relief of pain and suffering is a tribute to the ideas and work of many
dedicated investigators. Much of that work is presented in this text.
Despite our ability to treat some of these diseases through enzyme replacement therapy
(ERT) and, accurately define different diseases that look alike, there is much to be learned
about lysosomal disease. With each step up the barrier to knowledge, a new point of view
is attained, a fresh perspective. Much is seen more clearly and many “allegories of the
cave” are dispelled forever. Yet, our new view demands a new vision drawing us to find
better definitions of what we see. This is how it has been with lysosomal diseases. No
sooner had the little vesicle been described when a defect in it was shown to cause
a human disease. With each advance came the hope for better diagnosis and visions of
therapy. Nowhere was its value more evident than in the clear separation of the mucopoly-
saccharidoses into reliable diagnostic categories according to the enzyme that was deficient
in them. Long-standing debates and controversies were settled forever.
Still though, as in all lysosomal storage disease, what makes the difference in the
spectrum of iduronidase deficient disease from severe Hurler syndrome to mild Scheie
disease remains to be defined. There is no doubt that multiple genes are involved in these
complex diseases. Just when we thought that they were monogeneic, whole new visions
of the diseases have emerged. One even suggests that lysosomal storage may not be the
primary pathogenetic step, but rather, protesomal activation in an attempt to rid the cell
of improperly folded lysosomal enzyme. The universality of this theory remains to be
demonstrated. However, this new approach may provide another tool in the physician’s
bag to define and treat disease. It is with this enthusiasm that we should look forward to
new definitions of the lysosome and lysosomal disease. This text provides a thoughtful intro-
duction to a wide variety of data, concepts, and approaches to lysosomal storage disorders.
John A. Barranger
University of Pittsburgh, Pittsburgh, PA
May 2007
Contents
Preface ..............................................................................................................................vii
Contributors ..................................................................................................................... xiii
Chapter 1. From Lysosomes to Storage Diseases and Back:
A Personal Reminiscence ..............................................................................1
Christian de Duve
Chapter 2. Lysosomal Biogenesis and Disease ...............................................................7
Doug Brooks and Emma Parkinson-Lawrence
Chapter 3. The Concept of Treatment in Lysosomal Storage Diseases ........................37
Roscoe O. Brady
Chapter 4. Complex Lipid Catabolism .........................................................................45
Roscoe O. Brady and Roscoe O. Brady, Jr.
Chapter 5. Retroviral Vectors for Gene Therapy ..........................................................53
Seon-Hee Kim and Paul D. Robbins
Chapter 6. Adenovirus in Gene Therapy ......................................................................69
Angela Montecalvo, Andrea Gambotto, and Leonardo D’Aiuto
Chapter 7. Setting Back the Clock: Adenoviral-Mediated Gene Therapy
for Lysosomal Storage Disorders ................................................................81
Dolan Sondhi, Neil R. Hackett, Stephen M. Kaminksy,
and Ronald G. Crystal
Chapter 8. Adeno-Associated Viral-Mediated Gene Therapy of Lysosomal
Storage Disorders ........................................................................................97
Mario A. Cabrera-Salazar and Seng H. Cheng
Chapter 9. Herpes Simplex Virus Vectors for Gene Therapy of Lysosomal
Storage Disorders ......................................................................................111
Edward A. Burton and Joseph C. Glorioso
x Contents
Chapter 10. Gene Therapy of Lysosomal Storage Disorders by
Lentiviral Vectors ......................................................................................133
Alessandra Biffi and Luigi Naldini
Chapter 11. Substrate Reduction Therapy .....................................................................153
Frances M. Platt and Terry D. Butters
Chapter 12. Newborn Screening for Lysosomal Storage Disorders .............................169
C. Ronald Scott, Frantisek Turecek,
and Michael H. Gelb
Chapter 13. Genetic Counseling for Lysosomal Storage Diseases ...............................179
Erin O’Rourke, Dawn Laney, Cindy Morgan,
Kim Mooney, and Jennifer Sullivan
Chapter 14. Neural Stem Cell Therapy in Lysosomal Storage Disorders ....................197
Jean-Pyo Lee, Dan Clark, Mylvaganam Jeyakumar,
Rodolfo Gonzalez, Scott Mckercher, Franz-Josef Muller,
Rahul Jandial, Rosanne M. Taylor, Kook In Park,
Thomas N. Seyfried, Frances M. Platt, and Evan Y. Snyder
Chapter 15. The GM1 Gangliosidoses ..........................................................................217
Gustavo Charria-Ortiz
Chapter 16. The GM2 Gangliosidoses ..........................................................................229
Gustavo A. Charria-Ortiz
Chapter 17. Acid Sphingomyelinase-Deficient Niemann–Pick Disease ......................257
Edward H. Schuchmann, Margaret Mc Govern, Calogera
M. Simonaro, Melissa P. Wasserstein, and Robert J. Desnick
Chapter 18. Krabbe Disease (Globoid Cell Leukodystrophy) ......................................269
Junko Matsuda and Kunihiko Suzuki
Chapter 19. Metachromatic Leukodystrophy ................................................................285
Volkmar Gieselmann
Chapter 20. Fabry Disease ............................................................................................307
Roscoe O. Brady
Chapter 21. Gaucher Disease: Review and Perspectives on Treatment .......................319
Mario A. Cabrera-Salazar and John A. Barranger
Contents xi
Chapter 22. Therapeutic Goals in the Treatment of Gaucher Disease ..........................345
Neal Weinreb
Chapter 23. The Neuronal Ceroid Lipofuscinoses: Clinical Features
and Molecular Basis of Disease ................................................................371
Beverly L. Davidson, Mario A. Cabrera-Salazar, and David A. Pearce
Chapter 24. Mucopolysaccharidosis I ...........................................................................389
Lorne A. Clarke
Chapter 25. Mucopolysaccharidosis II (Hunter Syndrome) ..........................................407
Lorne A. Clarke
Chapter 26. Sanfilippo Syndrome: Clinical Genetic Diagnosis and Therapies ............415
John J. Hopwood
Chapter 27. Mucopolysaccharidosis IV (Morquio Syndrome) ..................................... 433
Shunji Tomatsu, Adriana M. Montaño, Tatsuo Nishioka,
and Tadao Orii
Chapter 28. Mucopolysaccharidosis Type VI
(Maroteaux–Lamy Syndrome) ..................................................................447
J. E. Wraith
Chapter 29. Mucopolysaccharidosis Type VII (Sly Disease): Clinical, Genetic
Diagnosis and Therapies ...........................................................................457
Denise J. Norato
Chapter 30. Pompe Disease-Glycogenosis Type II: Acid Maltase Deficiency ............473
Arnold Reuser and Marian Kroos
Chapter 31. Lysosomal Free Sialic Acid Storage Disorders: Salla
Disease and ISSD ......................................................................................499
Amanda Helip-Wooley, Robert Kleta, and William A. Gahl
Chapter 32. Cystinosis ..................................................................................................513
Robert Kleta, Amanda Helip-Wooley, and William A. Gahl
Chapter 33. I-Cell Disease ............................................................................................529
Doug Brooks, Chris Turner, Viv Muller, John Hopwood,
and Peter Meikle
Index ...............................................................................................................................539
Contributors
John A. Barranger
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA,
xiv Contributors
Seng H. Cheng
Genetic Diseases Science, Genzyme Corporation, Framingham, MA 01701-9322, USA,
