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Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures
P Vanherpe1, S Fieuws2, A D'Hondt1
1Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Background:
Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT).
Methods:
We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010-2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine.
Results:
In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05).
Conclusions:
Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.
Insights
Late-onset Pompe disease (LOPD) is a rare genetic disorder. This study highlights a long diagnostic delay and shows the 6-minute walk distance (6MWD) is a sensitive measure for tracking LOPD progression.
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Late-onset Pompe disease (LOPD) is a rare, progressive, hereditary neuromuscular disorder.
- LOPD results from mutations in the acid alpha-glucosidase (GAA) gene, leading to muscle weakness and respiratory issues.
- Enzyme replacement therapy (ERT) is the primary treatment for LOPD.
Purpose of the Study:
- To investigate the clinical, neuroimaging, and genetic characteristics of LOPD patients in Belgium.
- To assess the sensitivity of various outcome measures for monitoring LOPD progression over time.
- To determine the prevalence and diagnostic delay associated with LOPD in the Belgian population.
Main Methods:
- A longitudinal study of 52 Belgian LOPD patients over 7 years (2010-2017).
- Clinical assessments included limb-girdle muscle strength, respiratory function (FVC), and ambulation (6MWD, 10MWT).
- Neuroimaging, genetic analysis (GAA gene mutations), and patient-reported outcomes (ActivLim) were also performed.
Main Results:
- LOPD prevalence in Belgium was found to be 3.9 per million.
- The mean age of onset was 28.9 years, with a significant diagnostic delay averaging 12.9 years.
- Significant declines were observed in 6-minute walk distance (6MWD), MRC sum score, and forced vital capacity (FVC), indicating disease progression. The ActivLim score and 10-meter walk test (10MWT) did not show significant changes.
Conclusions:
- Increased awareness of LOPD is crucial due to the prolonged diagnostic delay.
- The 6-minute walk distance (6MWD) is identified as a sensitive outcome measure for monitoring LOPD.
- The study identified two novel GAA mutations and confirmed the high prevalence of the c.-32-13 T>G mutation in the Belgian cohort.
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