Research
Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study
1 Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, ’s-Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands
2 Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC – Sophia Children’s Hospital, University Medical Center, Rotterdam, the Netherlands
3 Department of Epidemiology and Biostatistics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4 Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands
5 Department of Neurology, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Utrecht, the Netherlands
6 Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands
7 Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
8 Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands
9 Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands
10 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
Orphanet Journal of Rare Diseases 2012, 7:88 doi:10.1186/1750-1172-7-88
Published: 12 November 2012Abstract
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.
