Supplementary Material for: Perinatal-onset neuronopathic Gaucher disease is refractory to high-dose ambroxol: A case report and literature review

Introduction: High-dose ambroxol is an effective pharmacological chaperone therapy for the systemic and neurological symptoms of Gaucher disease (GD). However, no clinical evidence of perinatal-onset GD has been documented. Case presentation: The patient had perinatal-onset neuronopathic GD (PnGD) and received high-dose ambroxol, beginning at 10 days of life after a newborn screening report. There was a transient hematological response after combined ambroxol and enzyme replacement therapy; however, laryngospasm, epileptic seizures, liver dysfunction, and heart failure progressed. The patient died 95 days after birth. Genetic testing revealed a homozygous L483R variant in GBA1. A literature review of 56 patients with nGD confirmed poor survival outcomes for patients with PnGD. Conclusion: Ambroxol therapy may be insufficient to improve the prognosis of patients with PnGD, underscoring the limitations of early intervention in newborn-screened patients with GD. Therefore, pre-emptive therapeutic strategies are required to rescue and cure neonates with PnGD.

引言：高剂量氨溴索（ambroxol）是治疗戈谢病（Gaucher disease, GD）全身症状与神经系统症状的有效药理分子伴侣疗法（pharmacological chaperone therapy）。然而目前尚未有围生期起病戈谢病的临床证据被记录。病例报告：该患者为围生期起病神经病变型戈谢病（perinatal-onset neuronopathic GD, PnGD），在新生儿筛查结果回报后，于出生后10天开始接受高剂量氨溴索治疗。联合氨溴索与酶替代疗法（enzyme replacement therapy）后，患者出现一过性血液学应答，但随后喉痉挛、癫痫发作、肝功能异常及心力衰竭病情进展。患者于出生后95天死亡。基因检测显示患者GBA1基因存在纯合子L483R变异。针对56例神经病变型戈谢病患者的文献回顾证实，围生期起病型患者的生存结局较差。结论：氨溴索疗法或不足以改善围生期起病神经病变型戈谢病患者的预后，这凸显了对新生儿筛查检出的戈谢病患者开展早期干预的局限性。因此，亟需采取抢先治疗策略以挽救并治愈围生期起病神经病变型戈谢病新生儿。