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). 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. 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). 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.

中文翻译：

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比利时晚发性庞贝病（LOPD）：临床特征和预后评估。

迟发性庞贝病（LOPD）是一种罕见的遗传性进行性疾病，通常以肢带肌肉无力和/或呼吸功能不全为特征。LOPD是由酸性α-葡萄糖苷酶（GAA）基因突变引起的，并通过酶替代疗法（ERT）进行治疗。我们研究了比利时晚发庞贝病患者（N = 52）的临床，脑影像学和遗传学特征，并探讨了在7年（2010-2017年）的纵向期间不同结果指标的敏感性，包括活动限制ActivLim评分，6分钟步行距离（6MWD），10 m步行测试（10MWT），MRC总和评分和坐卧/仰卧位强迫肺活量（FVC）。在比利时，我们计算出的LOPD患病率为3.9 /百万。52名LOPD患者的平均发病年龄为28.9岁（标准差：15.8岁），从7个月到68年不等。最初表现为肢带无力的患者中有百分之七十五（N = 39），而只有13％（N = 7）的呼吸道症状是最初的症状。无创通气（NIV）开始于37％（N = 19），平均年龄为49.5岁（SD：11.9 y），症状发作后的平均持续时间为15年（SD：10.2 y）。脑部影像学检查显示25％（N = 8）的患者存在异常，两名患者存在小脑动脉瘤，另外两名患者存在椎基底动脉的小肠扩张。平均诊断延迟时间为12.9年。所有患者均为复合杂合子，其中最常见的突变为c.-32-13 T> G，占96％。我们在GAA中发现了两个新的突变：c.1610_1611delA和c.186dup11。对于6MWD，MRC总分，FVC坐姿和FVC仰卧位，我们测量到随着时间的推移显着下降（p = 0.0002，p = 0.0001，p = 0.0077，p = 0.0151），而ActivLim评分和10MWT并未显示出这一下降（p> 0.05）。由于较长的诊断延迟，因此应进一步提高对LOPD的意识。6MWD（而不是ActivLim评分）是随访LOPD患者的敏感结果指标。