Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures

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. 1610₁611delA 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.