Newborn screening and therapies for Pompe disease (glycogen storage disease type II, acid maltase deficiency) will continue to expand in the future. It is thus important to determine whether enzyme activity or type of pathogenic genetic variant in GAA can best predict phenotypic severity, particularly the presence of infantile-onset Pompe disease (IOPD) versus late-onset Pompe disease (LOPD). We performed a retrospective analysis of 23 participants with genetically-confirmed cases of Pompe disease. The following data were collected: clinical details including presence or absence of cardiomyopathy, enzyme activity levels, and features of GAA variants including exon versus intron location and splice site versus non-splice site. Several combinations of GAA variant types for individual participants had significant associations with disease subtype, cardiomyopathy, age at diagnosis, gross motor function scale (GMFS), and stability of body weight. The presence of at least one splice site variant (c.546 G > C/p.T182 = , c.1076–22 T > G, c.2646 + 2 T > A, and the classic c.−32–13T > G variant) was associated with LOPD, while the presence of non-splice site variants on both alleles was associated with IOPD. Enzyme activity levels in isolation were not sufficient to predict disease subtype or other major clinical features. To extend the findings of prior studies, we found that multiple types of splice site variants beyond the classic c.−32–13T > G variant are often associated with a milder phenotype. Enzyme activity levels continue to have utility for supporting the diagnosis when the genetic variants are ambiguous. It is important for newly diagnosed patients with Pompe disease to have complete genetic, cardiac, and neurological evaluations.

庞贝病（II型糖原贮积病，酸性麦芽糖酶缺乏症）的新生儿筛查和治疗将在未来继续扩大。因此，重要的是确定GAA中的酶活性或致病性遗传变异类型是否可以最好地预测表型严重程度，特别是婴儿型庞贝病 (IOPD) 与晚发型庞贝病 (LOPD) 的存在。我们对 23 名经基因确诊的庞贝病患者进行了回顾性分析。收集了以下数据：临床细节，包括是否存在心肌病、酶活性水平以及GAA变体的特征，包括外显子与内含子位置以及剪接位点与非剪接位点。GAA的几种组合个体参与者的变异类型与疾病亚型、心肌病、诊断年龄、粗大运动功能量表 (GMFS) 和体重稳定性显着相关。存在至少一个剪接位点变体（c.546 G > C/p.T182 = ，c.1076–22 T > G，c.2646 + 2 T > A，以及经典的 c.−32–13T > G 变异）与 LOPD 相关，而两个等位基因上非剪接位点变异的存在与 IOPD 相关。单独的酶活性水平不足以预测疾病亚型或其他主要临床特征。为了扩展先前研究的结果，我们发现经典 c.-32-13T > G 变体之外的多种剪接位点变体通常与较温和的表型相关。当遗传变异不明确时，酶活性水平继续用于支持诊断。对新诊断的庞贝病患者进行完整的基因、心脏和神经系统评估非常重要。