Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the acid β-glucosidase encoding gene (GBA1), resulting in the deficient activity of acid β-glucosidase (GCase). To date, there is no approved treatment for the neurological manifestations of the disease. The role of Ambroxol as a chaperone for mutant GCase has been extensively demonstrated in vitro. Furthermore, different authors have reported beneficial effects of high doses of Ambroxol on neurological manifestations in patients affected by GD.

In this report, we describe the in vitro and in vivo effects of Ambroxol in two patients (P1 and P2) affected by the neurological form of GD and epilepsy, carrying mutations already reported as responsive to the chaperone. Indeed, P1 presented the N188S mutation in compound heterozygous with a null allele (IVS2 + 1G > A) and P2 was homozygous for the L444P mutation. As expected, a beneficial effect of Ambroxol was observed in cultured fibroblasts as well as in vivo, both on epilepsy and on biomarkers of GD, in P1. However, Ambroxol was completely undefective in P2, suggesting that other factors besides the GBA1 mutation itself would be involved in the response therapy which would be difficult to predict based on the patient genotype. The present report expands the experience of Ambroxol treatment in neurological GD patients and highlights the need to in vitro test the individual response to Ambroxol even in patients carrying mutations already classified as responsive to the chaperone.

高雪氏病（GD）是一种常染色体隐性溶酶体贮积病，由酸性β-葡萄糖苷酶编码基因（GBA1）的突变引起，导致酸性β-葡萄糖苷酶（GCase）的活性不足。迄今为止，还没有针对该疾病的神经系统表现的批准的治疗方法。氨溴索作为突变GCase的伴侣的作用已在体外得到广泛证明。此外，不同的作者报告了高剂量的氨溴索对受GD影响的患者的神经系统表现的有益作用。

在本报告中，我们描述了氨溴索在GD和癫痫症的神经系统形式影响的两名患者（P1和P2）中的体外和体内作用，这些突变携带据报道对伴侣起反应的突变。实际上，P1在具有等位基因无效的杂合子中出现了N188S突变（IVS2 + 1G> A），而P2对L444P突变是纯合的。如预期的那样，在培养的成纤维细胞中以及在体内观察到氨溴索对P1的癫痫和GD的生物标志物都有有益的作用。但是，氨溴索在P2中完全无缺陷，这表明除GBA1以外的其他因素突变本身将参与反应治疗，这将很难根据患者的基因型进行预测。本报告扩展了神经系统GD患者中氨溴索治疗的经验，并强调了需要体外测试个体对氨溴索的反应的需求，即使在携带已被分类为对伴侣起反应的突变的患者中也是如此。