Marloes Hagemans Pompe disease in children and adults: natural course, disease severity and impact on daily life Results from an international patient survey Pompe disease in children and adults: natural course, disease severity and impact on daily life Results from an international patient survey Marloes Hagemans The studies described in this thesis were performed at Erasmus MC University Medical Center Rotterdam, the Netherlands and were financially supported by the Princess Beatrix Fund, the International Pompe Association and Genzyme Corp., Boston, MA. The printing of this thesis was sponsored by Genzyme Europe B.V. and the International Pompe Association. ISBN: 90-9020644-2  M.L.C. Hagemans, 2006 All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without the prior written permission of the author. The copyright of the publications remains with the publishers. Layout: Tom de Vries Lentsch Cover photography: Peter Nicolai Cover design: Lennart Nicolai, Tom de Vries Lentsch Printed by: PrintPartners Ipskamp, Enschede Pompe disease in children and adults: natural course, disease severity and impact on daily life Results from an international patient survey De ziekte van Pompe bij kinderen en volwassenen: natuurlijk beloop, ernst van de ziekte en invloed op het dagelijks leven Resultaten van een internationale patiëntensurvey Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. S.W.J. Lamberts en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 21 juni 2006 om 9.45 uur door Maria Louise Catharina Hagemans geboren te Terneuzen Promotiecommissie Promotor: Prof.dr. A.J. van der Heijden Overige leden: Prof.dr. P.A. van Doorn Prof.dr. M.F. Niermeijer Prof.dr.ir. C.M. van Duijn Copromotoren: Dr. A.T. van der Ploeg Dr. A.J.J. Reuser Objectives and scope 7 Chapter 1 9 Introduction 10 1.1 Clinical aspects of Pompe disease 20 1.2 Research on rare disorders 22 1.3 Aims and outline of the thesis Chapter 2 31 The IPA/ Erasmus MC Pompe survey 32 2.1 Study design 36 2.2 Choice of assessment scales Chapter 3 45 The natural course of non-classic Pompe disease; a review of 225 published cases J Neurol 2005;252(8):875-884 Chapter 4 63 Clinical manifestation and natural course of late-onset Pompe disease in 54 Dutch patients Brain 2005;128(Pt 3):671-677 Chapter 5 79 Disease severity in children and adults with Pompe disease related to age and disease duration Neurology 2005; 64(12):2139-2141 Chapter 6 87 Course of disability and respiratory function in untreated late-onset Pompe disease Neurology 2006; 66(4):581-583 Chapter 7 95 Late-onset Pompe disease primarily affects quality of life in physical health domains Neurology 2004;63(9):1688-1692 Chapter 8 109 Fatigue: an important feature of late-onset Pompe disease Submitted Chapter 9 119 Impact of late-onset Pompe disease on daily life and participation Submitted Chapter 10 133 General discussion 134 10.1 Main findings 139 10.2 Methodological considerations 142 10.3 Future perspectives Appendix 155 Summary 185 Samenvatting 191 Curriculum vitae 197 List of publications 198 List of abbreviations 200 Dankwoord 201 Contents 7 Objectives and scope Pompe disease is a lysosomal storage disorder caused by deficiency of the enzyme acid α-glucosidase and mainly characterized by progressive skeletal muscle weakness. Research on this so far untreatable disease has long been directed towards unraveling the pathophysiological mechanisms and the development of a causal treatment. At the advent of enzyme replacement therapy, the research described in this thesis was intended to include the patient’s perspective in the assessment of the consequences of the disease. The aims were to map out the health status of patients with non-classic or late-onset Pompe disease, to provide more insight in the natural course and rate of progression on a group level, and to evaluate the use of specific self-report measurement scales. These studies form the basis for further follow-up of patients before and after the start of therapy, and are examples of a successful cooperation between patients, patient organizations and universities. Chapter 1 Introduction 9 [...]... documentation of the disease severity and progression The clinical and genetic heterogeneity of the non-classic or late-onset forms of Pompe disease have long been known, but data on the natural course are still scarce and depend on limited numbers of patients These considerations led us to set up a questionnaire survey among children and adults with Pompe disease, with the aim of gathering as much information... Pompe survey 31 Chapter 2 2.1 STUDY DESIGN The IPA/ Erasmus MC Pompe survey is an ongoing international study in which information is collected on disease history and current status of children and adults with Pompe disease by means of self-report questionnaires The recruitment of patients, collection of informed consent forms, and the distribution and collection of the questionnaires takes place in. .. changes in their clinical situation Questionnaires The IPA/ Erasmus MC Pompe survey comprised a baseline questionnaire on medical history and current condition developed specifically for patients with Pompe disease This Pompe Questionnaire’ was completed for both children and adults and the results were used to study the natural course of the disease and the disease severity in the patient population The... 2 Our findings with respect to the natural course of late-onset Pompe disease start with a review of published case reports in chapter 3, followed in chapter 4 by a detailed description of the natural history and clinical condition of the Dutch participants in the survey In chapter 5, the relation between disease severity and other patient characteristics in the international study population is described... protocols for the confirmation of Pompe disease vary between countries and laboratories and in time Therefore, no specific requirements were adopted for the way in which the patients in the IPA/ Erasmus MC Pompe survey were diagnosed In the Netherlands the variation in diagnostic methods is limited, since there has always been a strong research interest in Pompe disease and exchange of information between... followup of a patient and across the different centers contributing to the database 1.3 AIMS AND OUTLINE OF THE THESIS In 2002 the need to enhance the understanding of the variability, progression and natural history of Pompe disease, and in particular of the non-classic or late-onset form, was recognized by Erasmus MC and the International Pompe Association (IPA), a federation of patient groups worldwide.136... prospective information on the progression of the disease by presenting the results of the first two years of followup Chapters 7-9 focus on the results of specific assessment scales: health-related quality of life, fatigue, and the impact of Pompe disease on the daily life of the patients Chapter 10 provides a general discussion of the findings described in this thesis, the pros and cons of our approach, and. .. was realized that especially in rare disorders like Pompe disease data on the natural course are essential to evaluate any form of future treatment This led to the development of the IPA/ Erasmus MC Pompe survey, an ongoing international study on the clinical condition of children and adults with Pompe disease in which information is collected by means of self-report questionnaires Specific for this... the Pompe questionnaire is described in more detail in the ‘Patients and methods’ section of chapter 4 In the following section, the choice of assessment scales for the follow-up of patients with Pompe disease is discussed Table 2 Questionnaires included in the IPA/ Erasmus MC Pompe survey Baseline 1- and 2-year follow-up 3-year follow-up International study population Dutch subgroup International... place in close cooperation between Erasmus MC and the national patient organizations affiliated with the International Pompe Association (IPA) In a subgroup of patients longitudinal data were obtained in a yearly follow-up Based on the results from this subgroup, we have expanded the longitudinal data collection to all participants, starting in the third year after the baseline survey was completed . Hagemans Pompe disease in children and adults: natural course, disease severity and impact on daily life Results from an international patient survey Pompe disease. Lentsch Printed by: PrintPartners Ipskamp, Enschede Pompe disease in children and adults: natural course, disease severity and impact on daily life Results