Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study
Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study
复制标题
DOI：
10.1159/000514507
复制
发表时间：
2021-04-06
影响因子：
1.7
通讯作者：
Kumar, Sathish
中科院分区：
文献类型：
--
作者：
Barney, Anitha M.;Danda, Sumita;Kumar, Sathish
前言：高谢病是一种罕见的常染色体隐性遗传性溶酶体储存障碍，其致病基因的双等位变异导致葡萄糖神经酰胺酶功能缺陷，导致细胞内葡萄糖脑苷沉积。GD有3种主要类型，即非神经病型(I型)、急性神经病型(II型)和慢性神经病型(III型)。明确的治疗选择是有限的，也是昂贵的。如果不治疗，他们会很早就死于这种疾病。来自印度次大陆的研究很少，这些研究得出了导致他们过早死亡的因素。材料和方法：在南印度的一个三级护理环境中进行了一项回顾性研究，以评估2004年至2019年期间GD患者的临床概况、突变谱和各种处理策略(仅支持治疗、酶替代治疗[ERT]、底物减少治疗[SRT]造血干细胞移植[HSCT])以及死亡率预测因素。绘制了Kaplan-Meier生存曲线。在电子计算机中，对新的变种进行了预测。结果：在15年的研究期间，共有60名所有类型的GD患者。他们确诊时的中位年龄为2岁。中位随访期为5年(四分位数范围[IQR]=2~8)。总体死亡率为35%；然而，在接受明确治疗的人中，这一比例仅为10%。在那些只接受支持性治疗的患者中，死亡率高出4倍以上(47.5%)。确诊后中位生存期为6.3年(IQR=3.5~10.8)，支持治疗组为3.5年(IQR=1~5)。Kaplan-Meier生存分析显示两组间的死亡率差异有统计学意义(p值0.001)。多因素Logistic回归分析发现，神经病类型(OR=5)和单纯支持治疗(OR=6.3)是早逝的独立危险因素。结论：GD是一种少见疾病，如不及时治疗，死亡率较高。ERT和SRT是提高生存率的有效治疗方法。在资源有限的印度，神经病变类型的患病率较高，由于HSCT的一次性干预和成本，假设其疗效与ERT相似，HSCT可能是更合适的最终治疗选择。然而，造血干细胞移植在GD中的有效性和安全性还需要通过大量接受它的患者来进一步证实。
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.