Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease

Erasmus MC, University Medical Center, Department of Neurology, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Neuromuscular Disorders (Impact Factor: 2.64). 02/2009; 19(2):113-7. DOI: 10.1016/j.nmd.2008.11.007
Source: PubMed


To determine the rate of disease progression in patients with late-onset Pompe disease, we collected longitudinal data on pulmonary function and skeletal muscle strength in 16 patients whose symptoms had started in childhood or adulthood. The mean duration of follow-up was 16 years (range 4-29 years). During the follow-up period, eight patients (50%) became wheelchair bound and three (19%) became ventilator dependent. At a group level, pulmonary function deteriorated by 1.6% per year, and proximal muscle weakness progressed gradually. At the individual level, however, the rate and extent of progression varied highly between patients. In two thirds of patients, pulmonary function and muscle strength declined simultaneously and to the same extent. The remaining one third of patients showed a variable, sometimes rapidly progressive course, leading to early respirator or wheelchair dependency. These individual differences, especially in pulmonary dysfunction, indicate the need for regular monitoring every 6-12 months depending on the rate of disease progression.

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    • "Evidence from studies in patients with untreated late-onset Pompe disease indicate that the expected change in % predicted FVC in the upright position and in the supine position range from −1.0% to −4.6% [5,7,36,46] and 1.3% to −5.5% [5,7,36], respectively, annually. At the rate of disease progression observed in untreated patients with late-onset Pompe disease, and assuming that the MCID for deterioration of the FVC is the same as for improvement in FVC reported in IPF patients, untreated late-onset Pompe patients would have clinically significant worsening of lung function within 2 years. "
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    ABSTRACT: Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. Clinical improvement was perceived by patients in 6 of the 10 studies. In 6 of the 9 late-onset Pompe disease studies, the changes from baseline in percentage change in predicted FVC were above or within the MCID established for respiratory diseases and the difference was perceived as either an improvement or stabilization by patients." with "In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be evaluated specifically in late-onset Pompe disease and alternative outcome measures more specific to neuromuscular disease considered.
    Orphanet Journal of Rare Diseases 10/2013; 8(1):160. DOI:10.1186/1750-1172-8-160 · 3.36 Impact Factor
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    • "Cardiac involvement is very rare and symptoms are dominated by significant involvement of skeletal muscles with a gradually progressing myopathy and respiratory insufficiency leading to varying degrees of disability associated to reduced life expectancy on average. Most patients requires use of a wheelchair and ventilatory assistance (3-5). However, the recent development of a specific treatment, in the form of enzyme replacement therapy is modifying the natural course of the illness. "
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    ABSTRACT: Glycogen storage disease type II - also called Pompe disease or acid maltase deficiency - is an autosomal recessive metabolic disorder, caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. Pompe disease is transmitted as an autosomal recessive trait and is caused by mutations in the gene encoding the acid α-glucosidase (GAA), located on chromosome 17q25.2-q25.3. The different disease phenotypes are related to the levels of residual GAA activity in muscles. The clinical spectrum ranging from the classical form with early onset and severe phenotype to not-classical form with later onset and milder phenotype is described.
    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 10/2013; 32(2):82-84.
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    • "We have previously reported long-term retrospective data on muscle strength and pulmonary function in 16 patients with Pompe disease. [15] While 12 of these patients participated in the current study, the present analyses were based solely on new, prospectively obtained data. "
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    ABSTRACT: Background Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of −1.3% point/year for manual muscle testing and of −2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast. Conclusions Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.
    Orphanet Journal of Rare Diseases 11/2012; 7(1):88. DOI:10.1186/1750-1172-7-88 · 3.36 Impact Factor
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