Book Description:
Mucopolysaccharidoses (MPS) are caused by a deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: Chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are eleven known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death.

Other clinical features include coarse facial features, corneal clouding, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, heart valvular disease and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis. Patients may need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy throughout their lifetime. Current measures to intervene in bone disease progression and CNS involvement are not perfect and palliative, and improved therapies are urgently required and are being proposed.

Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzymes to the brain and bones, especially avascular cartilage, to prevent or ameliorate the devastating neurological defects and skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion and damage, since the severity of CNS involvement and skeletal dysplasia is associated with the level of activity in a patient’s daily life.

For the maximum benefit of available therapies, early detection and intervention are critical. Newborn screening and diagnostic systems have been developed by using tandem mass spectrometry. We review the history of diagnosis and newborn screening as well. Overall, this book illustrates a to-date overview of the pathogenesis, diagnosis, biomarkers, screening, and updated therapies as well as their impact on MPS, including ERT, HSCT, gene therapy, and anti-inflammatory drugs. History and activities of MPS societies are also described. It is a comprehensive textbook meant to cover many areas in the field of MPS and appeals to a broad spectrum of readers including physicians, scientists, students, pharmaceutical companies, and MPS communities. (Nova Medicine and Health)

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Book Reviews

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“As the CEO Of the MPS Society in the UK I can say that this publication is a significant milestone in the campaign for awareness of MPS conditions. As a MPS dad it is wonderful to have literature that can be a source of accurate knowledge that can be relied upon.” - Bob Stevens, Group Chief Executive, Society for Mucopolysaccharide Diseases, MPS Commercial, Buckinghamshire, UK

“This comprehensive book presents a substantial body of international wisdom on mucopolysaccharide diseases. It is notable for the inclusion of the opinions of clinicians, scientists, caregivers and charities working in the sector. This is recommended reading for anyone interested in lysosomal disease pathology and treatment, with an emphasis on the mucopolysaccharidoses.” - Brian Bigger, Chairman, European Study Group on Lysosomal Diseases, Professor of Cell and Gene Therapy, Stem Cell & Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine, Manchestee, UK

"I would like to recommend this book to not only specialists of mucopolysaccharidoses but general physicians taking care of patients with mucopolysaccharidoses.” - Hiroyuki Ida,M.D.,Ph.D., President of JSIMD (Japanese Society for Inherited Metabolic Diseases)

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Table of Contents:
Preface

Abbreviations and Acronyms

Summary of Mucopolysaccharidoses

Clinical Pictures at a Glance
Tadao Orii, Saori C. Tomatsu and Honoka Fujitsuka
Diagnosis of MPS and ML at a Glance lix
Tadao Orii, Nivethitha Arunkumar and Shunji Tomatsu
Therapies for MPS at a Glance lxv
Shunji Tomatsu, Hui-hsuan Chen, Takeyuki Akiyama
and Virginia Tsai
VOLUME I

Chapter 1 Introduction: The History of Research for Mucopolysaccharidoses 1
Shunji Tomatsu, Christine Lavery, Roberto Giugliani,
Paul Harmatz, Maurizio Scarpa, Grzegorz Węgrzyn
and Tadao Orii

Chapter 2 Overview of Mucopolysaccharidoses:
Diagnosis, Natural History, Clinical Pictures 17
Roberto Giugliani, Shunji Tomatsu, Christine Lavery,
Paul Harmatz, Maurizio Scarpa, Grzegorz Węgrzyn
and Tadao Orii

Chapter 3 Epidemiology of Mucopolysaccharidoses 21
Shaukat A. Khan, Tadao Orii, Roberto Giugliani
and Shunji Tomatsu

Chapter 4 Diagnosis of Mucopolysaccharidoses:
When Should We Suspect Mucopolysaccharidosis,
Based Only on an Interview and Clinical Examination? 47
Anna Tylki-Szymańska

Chapter 5 Pathogenesis of Mucopolysaccharidoses:
Dysfunction of Lysosomes 61
Giancarlo Parenti and Alessandro Fraldi

Chapter 6 Inflammation and Its Role in the Lysosomal Storage Disorders 75
Calogera M. Simonaro

Chapter 7 Mechanisms of Neurodegeneration in Mucopolysaccharidoses 87
Grzegorz Węgrzyn, Joanna Jakobkiewicz-Banecka,
Magdalena Gabig-Ciminska, Anna Kloska, Marcelina Malinowska,
Marta Moskot, Ewa Piotrowska, Magdalena Narajczyk,
Zyta Banecka-Majkutewicz, Bogdan Banecki, Alicja Węgrzyn
and Karolina Pierzynowska

Chapter 8 Glycosaminoglycans: Biosynthesis, Degradation, and
Related Lysosomal Storage Disorders 115
Cinzia Maria Bellettato, Rosella Tomanin, Laura Rigon,
Alessandra Zanetti, Nicola Volpi and Maurizio Scarpa

Chapter 9 Mucopolysaccharidosis Type I:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 143
M. Verónica Muñoz-Rojas, Shaukat A. Khan and Roberto Giugliani

Chapter 10 Mucopolysaccharidosis Type II:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 165
Shunji Tomatsu, Francyne Kubaski, Molly Stapleton,
Yasuyuki Suzuki, Kenji O. Orii, Filippo Vairo,
Ana Carolina Brusius-Facchin, Sandra Leistner-Segal,
Maira Graeff Burin, Carolina Fischinger Moura de Souza
and Roberto Giugliani

Chapter 11 Mucopolysaccharidosis Type III:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 211
Grzegorz Węgrzyn, Karolina Pierzynowska,
Joanna Jakobkiewicz-Banecka, Magdalena Gabig-Ciminska,
Anna Kloska, Marcelina Malinowska, Ewa Piotrowska,
Jolanta Wierzba, Magdalena Narajczyk,
Zyta Banecka-Majkutewicz, Bogdan Banecki
and Alicja Węgrzyn

Chapter 12 Mucopolysaccharidosis Type IVA:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 235
Kazuki Sawamoto, Carlos J. Alméciga-Díaz, William Mackenzie,
Robert W. Mason, Tadao Orii and Shunji Tomatsu

Chapter 13 Mucopolysaccharidosis Type IVB:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 273
Katsumi Higaki and Haruaki Ninomiya

Chapter 14 Mucopolysaccharidosis Type VI:
Clinical Features, Biochemistry, Diagnosis, Genetics and Treatment 285
Paul Harmatz

Chapter 15 Mucopolysaccharidosis Type VII:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 315
Kenji E. Orii, Yasuyuki Suzuki, Toshiyuki Fukao, Tadao Orii,
Shunji Tomatsu and William S. Sly

Chapter 16 Mucopolysaccharidosis Type IX:
Clinical Features, Biochemistry, Diagnosis, Genetics,
and Treatment 339
Francyne Kubaski and Shunji Tomatsu

Chapter 17 Mucolipidoses: Clinical Features, Biochemistry, Diagnosis,
Genetics, and Treatment 351
Takanobu Otomo
Chapter 18 Mucopolysaccharidosis-Plus Syndrome:
A New Type of Mucopolysaccharidosis with
Severe Systemic Symptoms 375
Hidehito Kondo and Takanobu Otomo

Chapter 19 Clinical Endpoints 385
Michael Beck
VOLUME II

Chapter 20 Biomarkers for Mucopolysaccharidoses 397
Francyne Kubaski, Robert W. Mason, Tadao Orii
and Shunji Tomatsu

Chapter 21 Assessment of Brain Function and
Structure in Mucopolysaccharidoses 425
Elsa G. Shapiro, Julie Eisengart, Kathleen Delaney
and Igor Nestrasil

Chapter 22 Bone Mineral Density in MPS 465
Francyne Kubaski and Heidi H. Kecskemethy

Chapter 23 Therapies for Mucopolysaccharidoses: An Overview 477
Carlos J. Alméciga-Diaz, Johana Guevara, Angela J. Espejo,
Alexander Rodriguez, Olga Echeverri and Luis A. Barrera

Chapter 24 Hematopoietic Stem Cell Transplantation in
Mucopolysaccharidoses: The Effects and Limitations 513
Marta Serafini, Jaap Jan Boelens and Hiromasa Yabe

Chapter 25 Enzyme Replacement Therapy for Mucopolysaccharidoses:
The Effects and Limitations 535
Carlos J. Alméciga-Diaz and Luis A. Barrera

Chapter 26 Gene Therapy for Treatment of Mucopolysaccharidoses:
The Effects and Limitations 561
Haiyan Fu and Douglas M. McCarty

Chapter 27 Orthopedic Surgical Interventions in the Mucopolysaccharidoses 585
Klane K. White

Chapter 28 Management of Tracheal Obstruction in MPS 597
Jennifer Sumner, Shunji Tomatsu, Molly Stapleton,
Ryan R. Davies and Christian Pizarro

Chapter 29 Corneal Transplantation 619
Susanne Pitz and Ulrike Hampel

Chapter 30 Perioperative Airway Management of MPS Patients 629
Mary Theroux and Lauren W. Averill

Chapter 31 Newborn Screening for MPS Diseases by Direct Assay of Enzymes
in Dried Blood Spots by Tandem Mass Spectrometry 639
Michael H. Gelb, Arun Babu Kumar, Fan Yi, Yang Liu,
Naveen Chennamanen, Sophia Masi, Susan Elliot,
Frantisek Turecek and C. Ronald Scott

Chapter 32 Newborn Screening of Mucopolysaccharidoses:
Comparison of the Fluorometric Technique and
Tandem Mass Spectrometry for Enzyme Assay 647
Chih-Kuang Chuang, Hsuan-Chieh Liao, Hsiang-Yu Lin,
Chuan-Chi Chiang and Shuan-Pei Lin

Chapter 33 Newborn Screening and Biomarkers for
Mucopolysaccharidoses by GAG Assay 661
Francyne Kubaski, Harumi Osago, Robert W. Mason,
Seiji Yamaguchi, Hironori Kobayashi, Mikako Tsuchiya,
Tadao Orii and Shunji Tomatsu

Chapter 34 Depolymerization of GAGs by Methanolysis and
Analysis by Tandem Mass Spectrometry 685
Pamela Lavoie and Christiane Auray-Blais

Chapter 35 A List of Animal Models with Mucopolysaccharidoses 697
Margret L. Casal and Mark E. Haskins
Chapter 36 Guidelines for Management and Treatment 713
Hiroo Hoshina, Molly Stapleton and Hiroyuki Ida

Chapter 37 Hurdles in Access to High-Priced Orphan Drugs 727
Yvonne Schuller, Marieke Biegstraaten
and Carla E. M. Hollak

Chapter 38 MPS Societies and Activities 755
Christine Lavery and Terri L. Klein

Epilogue 773

Essays or Poems: “Living with MPS” 775

About the Editors 781

About the Authors 787

Index 811

395