Pain in adult patients with Pompe disease: A cross-sectional survey
Introduction
Pompe disease (glycogen storage disease type II) is a rare autosomal recessive metabolic myopathy caused by a deficiency of the enzyme acid α-glucosidase (GAA). The deficiency of this lysosomal enzyme results in glycogen storage, particularly in skeletal and respiratory muscles [1], [2]. In 2006, enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase was registered as a treatment for Pompe disease [3], [4], [5], [6]. In adult patients, ERT has improved and/or stabilized pulmonary function, and has also improved walking distance [7]. Without treatment, the foremost features of the disease in these patients are progressive loss of muscle and deteriorating respiratory function [8], [9], [10].
As well as effects on skeletal and respiratory muscle function, other important symptoms of Pompe disease include fatigue and scoliosis [11], [12]. While patients have referred to pain as a symptom of Pompe disease, the literature has so far devoted little attention to it. Although, overall, a focus on pain in neuromuscular disorders (NMD) is rather recent, it has become clear that pain can be a prominent feature of many different NMDs [13], [14], [15], [16], [17], and that it affects patients' quality of life and mental health [14], [16], [18]. Pain is also a highly prevalent symptom in lysosomal storage disorders such as Fabry and Gaucher disease [19], [20]; in McArdle's disease (glycogen storage disease type V), myalgia is one of the dominating features [21]. In patients with Pompe disease, it may thus be an overlooked symptom.
Few studies have described pain in Pompe patients. One study in German patients with ‘non-classic’ Pompe disease reported myalgia as an initial symptom in 18% of the patients [10]. In a second study of Dutch ‘non-classic’ Pompe patients, almost half the patients experienced pain, very often in the legs [8]. In both studies, pain was not the main focus, and only assessed with a single item question. If pain in Pompe disease is to be managed appropriately, its severity and nature should be well defined, as should its effect on patients' functioning and participation in daily life.
In this cross-sectional survey, we therefore assessed the prevalence, severity and characteristics of the pain experienced by 124 adult Pompe patients, comparing these variables with those in an age-matched control group. As our second research question, we investigated whether pain was associated with lower quality of life and participation, and also with anxiety and depressive symptoms.
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Patients and controls
Patients were either recruited through the German patient organization (Selbsthilfegruppe Glykogenose Deutschland e.V., n = 110) or through Erasmus MC University Medical Center (n = 98), which is the national referral center for Pompe disease in The Netherlands. Controls, who had to be free of Pompe disease, were either partners, relatives or acquaintances of Pompe patients or of other neuromuscular patients. Their age was approximately the same as that of the Pompe patients who had been recruited.
Response and patient characteristics
We invited 208 patients to participate in this survey, 124 of whom took part; 62 were Dutch and 62 were German. The overall response rate was 60%: 63% for the Dutch patients and 56% for the German patients. The demographic profiles are listed in Table 1. Patients had a median age of 53 years (range 19–74); median disease duration since onset of symptoms was 18 years (range 1–62). Fifty-six percent of patients were female. At the time of the survey, 81% of patients were receiving ERT, 12% had
Discussion
This is the first study to describe the prevalence and characteristics of pain in a large number of adult patients with Pompe disease. It is also one of the largest studies on pain in a specific neuromuscular disorder. We show that the prevalence of pain was significantly higher in patients with Pompe disease (45%) than in controls (27%). Nearly one Pompe patient in two had experienced pain in the previous 24 h, against just over 1 in 4 controls.
While the Pain Severity and Pain Interference
Conclusions
Although pain is not the dominant symptom of Pompe disease, this sample of Pompe patients clearly showed it to be a prevalent and debilitating symptom. As pain is generally a well-defined symptom for which many treatment options are possible, extra efforts should be made to manage it properly in this population. We suggest that research and clinical practice involving Pompe patients should identify and classify pain better, and should also adopt a mechanism-based treatment strategy.
Conflicts of interest and funding
FH and MD have received lecturers' fees from the Genzyme Corporation, a Sanofi Company. BS has received lecturer's fees from the Genzyme Corporation, a Sanofi Company, and is a member of the global advisory board for Pompe disease at the Genzyme Corporation. Research on Pompe disease at Erasmus MC is financially supported by the following parties: ZonMw — The Netherlands Organisation for Health Research and Development [project no. 152001005]; the Dutch TI Pharma initiative “Sustainable Orphan
Acknowledgments
The authors gratefully acknowledge the logistic support provided by Thomas Schaller, the chairman of the German section of the International Pompe Association (IPA), Selbsthilfegruppe Glykogenose Deutschland e.V., as well as the organizational support received from Rineke Nelisse and Coriene Catsman at the Center for Lysosomal and Metabolic Diseases at Erasmus MC University Medical Center. They also thank the treating physicians for their contribution, including Drs. Cornelia Kornblum, Ursula
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