Background: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations.
Methods: Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted.
Results: Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests.
Conclusions: The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.
5例中国晚发型Pompe病患者的7个GAA基因新发突变报道 摘要 背景：Pompe病是一种由酸性α-1，4-葡糖苷酶基因（GAA基因）突变引起的罕见的的糖原累积病，不同种族的Pompe病患者临床表型及基因型差异很大，且其临床表型-基因型相关性尚不明确。本研究旨在报告5例伴有新发GAA基因突变的中国晚发型Pompe病患者的临床、病理及基因突变特点。 方法：收集从1986年4月至2017年8月在我院诊断为糖原累积病的患者的临床及病理资料，提取患者冰冻肌肉标本DNA进行二代测序和基因突变分析。 结果：5例患者的发病年龄中位数为13岁，病程中位数为5年。患者主要表现为进展性四肢近端肌肉及中轴肌无力，其中1例患者出现了呼吸困难并需要呼吸机辅助呼吸。肌肉活检可见肌纤维出现大小及形态各异的空泡样变性，PAS及ACP染色阳性。基因检测共发现到10个GAA基因突变，其中7个为新发突变（c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG）。 结论：7个GAA基因新发突变扩展了晚发型Pompe病患者基因表达谱，并提示中国晚发型Pompe病患者有较强的遗传异质性。.
Keywords: Alpha-glucosidase; DNA Mutational Analysis; Genetic Heterogeneity; Glycogen Storage Disease Type II.