Pugliese Alessia, Porcino Mattia, Drago Selene Francesca Anna, Trimarchi Giuseppe, Rodolico Carmelo, Musumeci Olimpia, Toscano Antonio
Clinical and Experimental Medicine Department, University of Messina, Messina, Italy.
Department of Economy, University of Messina, Messina, Italy.
J Neurol. 2025 Jun 16;272(7):464. doi: 10.1007/s00415-025-13105-0.
Pompe disease is an inherited metabolic disorder, caused by acid alpha-glucosidase (GAA) enzyme deficiency. Late-onset form (LOPD) usually presents with proximal and axial myopathy, followed by progressive respiratory involvement. Since 2006, enzyme replacement therapy (ERT) has been the gold standard treatment. Recently, two ERTs of second generation have been approved. Several studies have demonstrated the benefits of the first generation ERT (FG-ERT), although outcomes are quite variable, and very long-term data are limited. In fact, functional long-term studies are still needed to clearly point out the prolonged efficacy of FG-ERT. We describe a cohort of 49 LOPD patients, providing a very long-term follow-up of motor and pulmonary function of 30 of them treated by FG-ERT (from 2 to 20 years), using 6MWT, FVC, and GSGC score to evaluate patients' responses. 6MWT remained quite stable in the first 4 years of therapy, followed by a slow decline of its value of about 21%. FVC showed an improving trend in the first 4 years, followed by a decline of about 12%. Along the follow-up, GSGC score worsened with an increasing of about 30% of the total score values. Although long-term results evidenced variable therapeutic responses, the general trend is an improvement in motor and respiratory functions during the first 2-4 years of treatment, followed by a variable degree of decline. According to these results, and in line with recent EPOC recommendations, it is strongly suggested to start therapy in symptomatic patients, but also to carefully manage presymptomatic patients to timely supply ERT treatment.
庞贝病是一种遗传性代谢紊乱疾病，由酸性α-葡萄糖苷酶（GAA）酶缺乏引起。晚发型（LOPD）通常表现为近端和轴索性肌病，随后逐渐出现呼吸功能受累。自2006年以来，酶替代疗法（ERT）一直是金标准治疗方法。最近，两种第二代ERT已获批准。多项研究已证明第一代ERT（FG-ERT）的益处，尽管结果差异很大，且长期数据有限。事实上，仍需要进行长期功能研究以明确指出FG-ERT的长期疗效。我们描述了一组49例LOPD患者，对其中30例接受FG-ERT治疗（2至20年）的患者的运动和肺功能进行了非常长期的随访，使用6分钟步行试验（6MWT）、用力肺活量（FVC）和全球严重程度分级（GSGC）评分来评估患者的反应。在治疗的前4年中，6MWT保持相当稳定，随后其值缓慢下降约21%。FVC在最初4年呈改善趋势，随后下降约12%。在整个随访过程中，GSGC评分恶化，总分值增加约30%。尽管长期结果显示治疗反应存在差异，但总体趋势是在治疗的前2至4年运动和呼吸功能有所改善，随后出现不同程度的下降。根据这些结果，并与最近的欧洲庞贝病临床研究（EPOC）建议一致，强烈建议对有症状的患者开始治疗，同时也要谨慎管理无症状患者，以便及时提供ERT治疗。
