戈谢病(GD)是一种常染色体隐性遗传性溶酶体贮积症,由于酸性β-葡萄糖苷酶(GCase)酶的活性不足,导致葡萄糖神经酰胺(GlcCer)及其脱酰基衍生物的逐渐溶酶体积累,葡萄糖鞘氨醇(GlcSph)。GCase由GBA1基因编码,位于高度同源的假基因上游的1q2116kb染色体上。迄今为止,已经报道了超过400种GBA1致病变体,其中许多源于基因和假基因之间的重组事件。在过去的几年里,获得新技术的增加导致提供GD检测的诊断实验室数量呈指数级增长。然而,GD的生化和基因诊断都具有挑战性,迄今为止,尚无针对GD实验室诊断的具体循证指南发表.本文提供的指南的目的是为GD诊断的生化和基因检测的技术实施和解释提供循证建议,以确保在全球范围内为GD患者提供及时和准确的诊断。该指南是由戈谢病国际工作组(IWGGD)诊断工作组的成员制定的,建立了一个非营利性网络,以促进GD的临床和基础研究,最终目的是改善该疾病患者的生活。IWGGD的目标之一是支持对GD诊断的公平访问并标准化程序以确保准确的诊断。因此,建立了一个由GD诊断领域的生物化学家和遗传学家组成的指南开发小组,并选择了要讨论的主题列表。在这些准则中,通过文献的系统回顾收集的信息提供了二十条建议,并提出了两种不同的诊断算法。考虑到获得诊断服务的地理差异。此外,我们发现了当前诊断工作流程中的几个漏洞,并在IWGGD中采取了措施来实现这些漏洞.我们认为,执行这些准则中提供的建议将促进公平,为全球GD患者提供及时准确的诊断。
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the deficient activity of the acid beta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer) and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromosome 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic variants have been reported, many of them derived from recombination events between the gene and the pseudogene. In the last years, the increased access to new technologies has led to an exponential growth in the number of diagnostic laboratories offering GD testing. However, both biochemical and genetic diagnosis of GD are challenging and to date no specific evidence-based
guidelines for the laboratory diagnosis of GD have been published. The objective of the
guidelines presented here is to provide evidence-based recommendations for the technical implementation and interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diagnosis for patients with GD worldwide. The
guidelines have been developed by members of the Diagnostic Working group of the International Working Group of Gaucher Disease (IWGGD), a non-profit network established to promote clinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One of the goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure an accurate diagnosis. Therefore, a
guideline development group consisting of biochemists and geneticists working in the field of GD diagnosis was established and a list of topics to be discussed was selected. In these
guidelines, twenty recommendations are provided based on information gathered through a systematic review of the literature and two different diagnostic algorithms are presented, considering the geographical differences in the access to diagnostic services. Besides, several gaps in the current diagnostic workflow were identified and actions to fulfill them were taken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines will promote an equitable, timely and accurate diagnosis for patients with GD worldwide.