Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q;D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a-half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients.

Gaucher疾病3型（GD3）是一种严重衰弱的疾病，其特征是多系统表现和神经退行性变。酶替代疗法可减轻内脏体征和症状，但对神经功能没有影响。已经建议使用氨溴索作为酶增强剂。一些研究已经证实其在预防神经性高雪氏病的神经学表现发展方面的有效性。在这项研究中，我们报告了两个GD3兄弟姐妹，其中氨溴索联合酶替代疗法在疾病的不同阶段开始。我们通过成纤维细胞研究的结果和两名患者的长期临床结果证明了氨溴索对L444P / H225Q; D409H葡萄糖脑苷脂酶活性的酶增强作用。被诊断为患有神经系统疾病的四岁半的同胞表现出氨溴索治疗的相对较快改善，随后病情稳定。在7周开始接受治疗的年轻同胞在7岁时表现出注意力缺陷和平均认知功能低下，但未表现出其他神经系统症状。神经学结果的差异表明，氨溴索延缓甚至阻止了年轻同胞神经系统表现的演变。该观察结果表明，氨溴索治疗的早期开始可能会阻止某些GD3患者的神经系统受累。在7周开始接受治疗的年轻同胞在7岁时表现出注意力缺陷和平均认知功能低下，但未表现出其他神经系统症状。神经学结果的差异表明，氨溴索延缓甚至阻止了年轻同胞神经系统表现的演变。该观察结果表明，氨溴索治疗的早期开始可能会阻止某些GD3患者的神经系统受累。在7周开始接受治疗的年轻同胞在7岁时表现出注意力缺陷和平均认知功能低下，但未表现出其他神经系统症状。神经学结果的差异表明，氨溴索延缓甚至阻止了年轻同胞神经系统表现的演变。该观察结果表明，氨溴索治疗的早期开始可能会阻止某些GD3患者的神经系统受累。