Late-onset Pompe disease: what is the prevalence of limb-girdle muscular weakness presentation?

ABSTRACT Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with “unexplained” limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an “unexplained” limb-girdle weakness even without vacuolar myopathy in muscle biopsy.

摘要：庞贝病（Pompe disease）是一种由酸性α-葡萄糖苷酶（acid alpha-glucosidase, GAA）缺乏所致的遗传性疾病。本项单中心观察性研究以巴西高危人群为研究对象，以干血斑试验（dried blood spot test）作为主要筛查工具，评估晚发型庞贝病的患病率。研究收集了24例肌肉活检未显示空泡性肌病、病因不明的肢带型肌无力患者的干血斑样本，用于GAA活性检测。对于酶活性降低的样本，进一步开展GAA基因突变检测。在24例干血斑样本中，1例患者（占比4.2%）的GAA酶活性偏低（NaG/AaGIA：40.42；%INH：87.22%）。针对该患者的基因分析证实其GAA基因存在2处杂合突变（c.-32-13T>G/p.Arg854Ter）。本研究结果提示，临床医师应对表现为"病因不明"的肢带型肌无力、且肌肉活检未显示空泡性肌病的患者排查晚发型庞贝病。