Trunk muscle involvement in late-onset Pompe disease: Study of thirty patients
Introduction
Pompe disease, also known as acid maltase deficiency (AMD) or glycogen storage disease type II (GSD II), is a rare autosomal recessive disorder due to a deficiency of the lysosomal enzyme acid alpha glycosidase (GAA). This deficiency causes intralysosomal accumulation of glycogen in several tissues such as skeletal muscle, cardiac muscle or liver [1]. Different clinical patterns have been described, ranging from rapidly progressive infantile forms to slowly progressive adult-onset phenotypes [2]. In general, late-onset Pompe disease is characterized by weakness of the proximal limb and axial muscles associated with respiratory muscles involvement [3]. However, many different clinical presentations have been reported, ranging from predominant respiratory involvement to exclusive limb muscles weakness.
Clinical and muscle biopsy findings can be unspecific in Pompe disease, so that muscle imaging can become a helpful diagnostic tool [1]. Computed tomography (CT) studies in adult patients have shown that the disease spreads over the years from trunk to extremities [4] with selective muscle involvement found in the thighs [5].
The most recent therapeutic progress in Pompe disease has been enzymatic replacement therapy (ERT) with recombinant human GAA (rh-GAA), which has proved to be effective in both infantile and adult forms [6], [7]. Although long-term follow-up data in treated patients are still lacking, ERT seems to improve muscle weakness and to stabilize the disease. The response to rh-GAA may be less robust in more advanced phases of the disease [8] and this emphasizes the need for prompt diagnosis and early treatment initiation. Because of the high costs of the treatment there have been controversial discussions about when the therapy should be started [9].
Considering that paravertebral muscles are involved at an early disease stage, we decided: (1) to study both the posterior and anterior trunk muscles in 30 late-onset Pompe patients by muscle imaging in order to evaluate their degree of involvement in a large cohort of patients at different functional stages; (2) to investigate whether there is a correlation between our clinical and imaging data.
Section snippets
Clinical data
A group of 30 adult-onset Pompe patients undergoing regular follow-up assessments at our centres was recruited from April 2006 to July 2011. Pompe disease diagnosis was based on <30% reduction versus controls of GAA activity in peripheral blood lymphocytes/muscle, and was confirmed by molecular analysis of the GAA gene (Table 1).
Muscle MRI was performed as part of the assessment and patients were classified into 4 groups according to the following functional stages:
- –
Asymptomatic: no muscle
Results
All patients (17 women and 13 men) had a late-onset form of the disease. All but 5 were symptomatic. Mean age at MRI was 46 years (±16.7 SD); mean age at disease onset was 29 years (±12.9 SD); mean delay in diagnosis was 10 years (±8.4 SD) and average duration of the symptoms at the time of imaging was 7 years (±12).
We classified 5 patients as asymptomatic (16.6%), 7 as mildly affected (23.3%), 11 as moderately affected (36.6%), and 7 as severely affected (23.3%) (Table 1).
Eleven out of thirty
Discussion
Pompe disease as a metabolic muscle disease has received a lot of radiologic attention in the last few years, especially in relation to the recent ERT introduction [4], [5], [8], [11], [12]. Muscular imaging, especially muscle MRI, has proved to be reliable in assessing both the pattern and the severity of muscle damage in several different muscle disorders [13], [14], [15], [16].
In particular, CT studies demonstrated that Pompe disease in adult patients spreads over the years from trunk to
Conflict of interest
None.
Acknowledgements
We thank Mary Bardon for her English support and the patients, without whom this study would not have been possible, for their patience.
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