Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. Materials and Methods: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. Results: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2–8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5–10.8) in the definite treatment group and 3.5 years (IQR = 1–5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. Conclusion: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.
Public Health Genomics

中文翻译：

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戈谢病的临床遗传学特征、治疗方式和死亡率预测因素：一项 15 年回顾性研究

简介：戈谢病 (GD) 是一种罕见的常染色体隐性溶酶体贮积症，其中葡糖苷酶 β 酸 ( GBA ) 基因中的双等位基因致病变异导致葡糖神经酰胺酶功能缺陷，导致葡糖脑苷脂沉积在细胞中。GD有3种主要类型，即非神经性（I型）、急性神经性（II型）和慢性神经性（III型）。确定的治疗选择是有限且昂贵的。如果不治疗，他们很早就死于这种疾病。很少有来自印度次大陆的研究，这些研究引发了导致他们过早死亡的因素。材料和方法：一项回顾性研究在印度南部的三级医疗机构进行，以评估临床特征、突变谱和各种管理策略（仅支持疗法、酶替代疗法 [ERT]、底物减少疗法 [SRT] 造血干细胞移植 [ HSCT])，以及 2004 年至 2019 年 GD 患者的死亡率预测因子。绘制了 Kaplan-Meier 生存曲线。对新变体进行了计算机模拟预测。结果：在 15 年的研究期间，共有 60 名患有所有类型 GD 的患者。他们诊断时的中位年龄为 2 岁。中位随访时间为 5 年（四分位距 [IQR] = 2-8）。总死亡率为 35%；然而，在接受明确治疗的患者中，这一比例仅为 10%。仅接受支持治疗的患者的死亡率 (47.5%) 高出 4 倍以上。明确治疗组从诊断时起的中位生存期为 6.3 年（IQR = 3.5-10.8），支持治疗组为 3.5 年（IQR = 1-5）。Kaplan-Meier 生存分析显示显着 ( p值 0.001) 这些组之间的死亡率差异。多元逻辑回归分析发现神经元类型（OR = 5）和仅支持疗法（OR = 6.3）是过早死亡的独立危险因素。结论： GD是一种罕见病，如果不及时治疗，死亡率很高。ERT 和 SRT 是提高生存率的最终治疗方法。在像印度这样资源有限的地区，由于神经病类型的患病率较高，HSCT 可能是更合适的最终治疗选择，因为其一次性干预和成本，假设疗效与 ERT 相似。然而，HSCT 在 GD 中的有效性和安全性需要通过接受它的大量患者进一步确定。
公共卫生基因组学