Objective

Enzyme replacement therapy (ERT), the only approved therapy for infantile-onset Pompe disease (IOPD), had heterogeneous clinical effects due to factors such as severity, age at first treatment, dosage, and dosing regimens. We report the clinical and biochemical outcomes of a cohort of IOPD patients identified through newborn screening, and evaluating the dosage effect.

Study design

A retrospective observational study was designed to describe the long-term clinical and biochemical outcomes of a uniform cohort of IOPD patients who have been treated with high-dosage of ERT.

Results

Twenty-eight patients received alglucosidase alpha at either the labeled dosage followed by a high dosage (n = 23) or a high dosage exclusively (n = 5). At a median age of 8.3 years (0.8–17.3), 15 patients were walkers, 8 were weak walkers, and 5 were nonwalkers. The three groups exhibited a significant difference in the age of gross motor decline (p < .001). In patients with classical IOPD diagnosed through newborn screening, those late in ERT initiation (p = .006) or late in high-dosage ERT initiation (p = .044) had a higher risk of motor decline. At the latest assessment, both serum creatine kinase (CK) and urinary glucose tetrasaccharide (uGlc4) levels were lowest in the walkers. During follow up, the biomarker levels, once rose, never returned to normal.

Conclusion

Low CK and uGlc4 levels were correlated with favorable response to ERT in IOPD patients, although CK may be more fluctuated than uGlc4. High-dose ERT instituted immediately at newborn screening seems to give the best outcome, and a dosage increase is necessary upon – or, even better, before – a rise in biomarker levels.

中文翻译：

---

早期和更高剂量的阿糖苷酶 α 可改善婴儿期庞贝病患者的预后：来自真实世界经验的证据。

客观的

酶替代疗法 (ERT) 是唯一获批的婴儿型庞贝病 (IOPD) 疗法，由于严重程度、首次治疗的年龄、剂量和给药方案等因素，具有异质的临床效果。我们报告了通过新生儿筛查确定的一组 IOPD 患者的临床和生化结果，并评估了剂量效应。

学习规划

一项回顾性观察研究旨在描述接受高剂量 ERT 治疗的 IOPD 患者的长期临床和生化结果。

结果

28 名患者接受了标记剂量的阿糖苷酶 α，然后是高剂量（n  = 23）或仅高剂量（n  = 5）。中位年龄为 8.3 岁（0.8-17.3），15 名患者是步行者，8 名是弱步行者，5 名是非步行者。三组在粗大运动衰退的年龄方面表现出显着差异（p  < .001）。在通过新生儿筛查诊断为经典 IOPD 的患者中，ERT 启动较晚（p  = .006）或高剂量 ERT 启动较晚（p = .044) 有更高的运动衰退风险。在最新的评估中，步行者的血清肌酸激酶 (CK) 和尿葡萄糖四糖 (uGlc4) 水平最低。在随访期间，生物标志物水平一旦上升，就再也没有恢复正常。

结论

低 CK 和 uGlc4 水平与 IOPD 患者对 ERT 的良好反应相关，尽管 CK 可能比 uGlc4 波动更大。在新生儿筛查中立即开始高剂量 ERT 似乎可以产生最佳结果，并且在生物标志物水平升高时（或者更好的是，在之前）增加剂量是必要的。