Spada Marco, Pagliardini Veronica, Ricci Federica, Biamino Elisa, Mongini Tiziana, Porta Francesco
Department of Pediatrics, University of Torino, Torino, Italy.
Department of Neuroscience, University of Torino, Torino, Italy.
J Pediatr Endocrinol Metab. 2018 Dec 19;31(12):1343-1347. doi: 10.1515/jpem-2018-0336.
Background With conventional enzyme replacement therapy (ERT), the clinical prognosis of classic Pompe disease is often unsatisfactory. About half the patients treated with ERT at the recommended dosage (20 mg/kg every other week) require ventilatory support within the first years of life. The heterogeneous response to ERT has been related to different factors, including cross-reactive immunologic material (CRIM) status and age at ERT initiation. Early treatment with a standard dosage of ERT improves clinical outcome and avoids mechanical ventilation in CRIM-positive patients detected at newborn screening, not preventing persistent hyperCKemia and muscle weakness. Later treatment with higher dosages of ERT was shown to provide similar benefits in CRIM-positive patients. Here, we report the clinical and biochemical outcomes of six patients with classic Pompe disease treated with different dosages of alglucosidase alpha at different ages. Methods A standard dosage of ERT was employed in five patients, sharing a poor prognosis after transient clinical improvements, even in the case of early treatment (four died at 22.2±11.9 months and one survived but required tracheostomy and gastrostomy). Early higher dosage of alglucosidase alpha (40 mg/kg/week from 14 days) was administered to one CRIM-positive patient with fetal persistent bradycardia. Results Early higher dosage of alclucosidase alpha not only achieved normal neuromotor development but also the full correction of biochemical markers of muscle damage until 3 years of age, an unmet target with the standard dosage. Speech delay was not prevented by this approach. Conclusions We suggest that early treatment with a higher dosage of ERT may further improve clinical prognosis in classic Pompe disease.
背景 采用传统酶替代疗法（ERT）时，经典型庞贝病的临床预后往往不尽人意。约一半接受推荐剂量（每两周20mg/kg）ERT治疗的患者在生命的头几年需要通气支持。对ERT的异质性反应与多种因素有关，包括交叉反应免疫物质（CRIM）状态和开始ERT治疗时的年龄。对新生儿筛查发现的CRIM阳性患者，早期使用标准剂量的ERT可改善临床结局并避免机械通气，但无法预防持续性高肌酸激酶血症和肌肉无力。后来的研究表明，对CRIM阳性患者使用更高剂量的ERT进行治疗也能带来类似的益处。在此，我们报告了6例经典型庞贝病患者在不同年龄接受不同剂量的α-葡萄糖苷酶治疗后的临床和生化结果。方法 5例患者采用标准剂量的ERT治疗，即使早期治疗，短暂的临床改善后预后仍较差（4例在22.2±11.9个月时死亡，1例存活但需要气管切开术和胃造口术）。对1例患有胎儿持续性心动过缓的CRIM阳性患者，从14天起给予早期高剂量的α-葡萄糖苷酶（40mg/kg/周）。结果早期高剂量的α-葡萄糖苷酶不仅实现了正常的神经运动发育，还在3岁前完全纠正了肌肉损伤的生化指标，这是标准剂量无法实现的目标。这种方法未能预防语言发育迟缓。结论 我们认为，早期使用更高剂量的ERT治疗可能会进一步改善经典型庞贝病的临床预后。
