Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1‐encoded enzyme, β‐glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High‐dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long‐term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long‐lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high‐dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long‐lasting effect of ambroxol‐based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

中文翻译：

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大剂量氨溴索治疗神经病性戈谢病快速且持久的疗效：病例报告和文献综述

戈谢病（GD）是一种溶酶体贮积症，由缺乏GBA1‐编码酶，β-葡萄糖脑苷脂酶。酶替代疗法对神经病性戈谢病（nGD）无效。高剂量氨溴索已作为一组 nGD 患者的替代治疗。然而，对于氨溴索治疗后患者的临床适应症和长期结果知之甚少。我们在此报告一例女性患者，她从 11 个月大起就出现 GD 2 型进行性疾病，并具有 p.L483P（以前定义为 p.L444P）和 p.R502H（p.R463H）的致病性变异。在GBA1。伊米苷酶与氨溴索的联合治疗在 1 周内开始改善患者的运动活动，同时将防止表型恶化的持久效果保持了 30 个月。一项文献综述确定了 40 名接受过大剂量氨溴索治疗的 nGD 患者。无论 p.L483P 纯合子、杂合子或其他基因型如何，超过 65% 的患者对分子伴侣治疗有良好反应。这些结果强调了基于氨溴索的伴侣疗法对具有扩大的突变谱的患者的长期效果。GBA1。