Neuromuscular Research Unit, Department of Neurology, University of Copenhagen, Copenhagen, Denmark.
Mol Genet Metab. 2013 Nov;110(3):287-9. doi: 10.1016/j.ymgme.2013.08.005. Epub 2013 Aug 15.
Late-onset Pompe disease is a rare, but potentially treatable metabolic myopathy, and therefore should not be overlooked. However, it is not unusual that patients go undiagnosed for many years. We hypothesized that patients with late-onset Pompe disease may have been overlooked in a population of patients with unclassified neuromuscular disease.
We used DBS (dried blood spots) to screen for Pompe disease in the two largest neuromuscular clinics and one of the main respiratory centers in Denmark. We selected patients with unclassified LGDM (limb-girdle muscular dystrophy), idiopathic elevation of creatine kinase, unexplained myopathy on muscle biopsy, unexplained restrictive respiratory insufficiency or unspecified myopathy for screening.
177 patients were found eligible for inclusion, and 103 (58.2%) patients accepted screening. Three patients with Pompe disease were identified with DBS, and subsequent genetic testing revealed known pathogenic mutations in the GAA gene. All three patients were found among 38 patients with unclassified LGMD (8%).
Our findings indicate that a DBS should be considered early in the diagnostic work-up of patients with an LGMD phenotype, to rule out Pompe disease. Retrospectively, all 3 patients presented with "red flags" more compatible with Pompe disease than LGMD, including; 1) mild non-dystrophic, myopathic features on muscle biopsy, 2) creatine kinase levels below 1000, and 3) disproportionate axial and respiratory muscle involvement in comparison with limb muscle involvement.
迟发性庞贝病是一种罕见但有潜在治疗效果的代谢性肌病，因此不应被忽视。然而，患者多年未被诊断的情况并不少见。我们假设在未分类的神经肌肉疾病患者人群中，可能忽略了迟发性庞贝病患者。
我们使用 DBS（干血斑）在丹麦最大的两个神经肌肉诊所和一个主要呼吸中心筛查庞贝病。我们选择未分类的 LGMD（肢带型肌营养不良症）、肌酸激酶升高、肌肉活检不明原因肌病、不明原因的限制性呼吸不足或未明确肌病的患者进行筛查。
发现 177 名患者符合纳入标准，其中 103 名（58.2%）患者接受了筛查。通过 DBS 发现了 3 名庞贝病患者，随后的基因检测显示 GAA 基因存在已知的致病性突变。这 3 名患者均在 38 名未分类的 LGMD 患者（8%）中发现。
我们的研究结果表明，在具有 LGMD 表型的患者的诊断工作中，应早期考虑进行 DBS，以排除庞贝病。回顾性分析，所有 3 名患者均表现出与 LGMD 相比更符合庞贝病的“危险信号”，包括：1）肌肉活检显示轻微的非营养不良性、肌病特征，2）肌酸激酶水平低于 1000，3）与肢体肌肉受累相比，轴向和呼吸肌受累不成比例。
