Impact of GLA Variant Classification on the Estimated Prevalence of Fabry Disease: A Systematic Review and Meta-Analysis of Screening Studies.

IF 6 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Genomic and Precision Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-04 DOI:10.1161/CIRCGEN.123.004252

Emanuele Monda, Gaetano Diana, Francesca Graziani, Marta Rubino, Athanasios Bakalakos, Ales Linhart, Dominique P Germain, Maurizio Scarpa, Elena Biagini, Maurizio Pieroni, Perry Mark Elliott, Giuseppe Limongelli

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引用次数: 0

Abstract

Background: The diagnosis of Fabry disease (FD) has relevant implications related to the management. Thus, a clear assignment of GLA variant pathogenicity is crucial. This systematic review and meta-analysis aimed to investigate the prevalence of FD in high-risk populations and newborns and evaluate the impact of different GLA variant classifications on the estimated prevalence of FD.

Methods: We searched the EMBASE and PubMed databases on February 21, 2023. Observational studies evaluating the prevalence of FD and reporting the identified GLA variants were included. GLA variants were re-evaluated for their pathogenicity significance using the American College of Medical Genetics and Genomics criteria and the ClinVar database. The pooled prevalence of FD among different settings was calculated. The study was registered on PROSPERO (CRD42023401663) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Results: Of the 3941 studies identified, 110 met the inclusion criteria. The pooled prevalence of FD was significantly different according to the clinical setting and criteria used for the pathogenicity assessment. Using the American College of Medical Genetics and Genomics criteria, the pooled prevalence was 1.2% in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy (26 studies; 10 080 patients screened), 0.3% in end-stage renal disease/chronic kidney disease (38 studies; 62 050 patients screened), 0.7% in stroke (25 studies; 15 295 patients screened), 0.7% in cardiac conduction disturbance requiring pacemaker (3 studies; 1033 patients screened), 1.0% in small-fiber neuropathy (3 studies; 904 patients screened), and 0.01% in newborns (15 studies; 11 108 793 newborns screened). The pooled prevalence was different if the GLA variants were assessed using the ClinVar database, and most patients with a discrepancy in the pathogenicity assignment carried 1 of the following variants: p.A143T, p.D313Y, and p.E66Q.

Conclusions: This systematic review and meta-analysis describe the prevalence of FD among newborns and high-risk populations, highlighting the need for a periodic reassessment of the GLA variants in the context of recent clinical, biochemical, and histological data.

Registration: URL: https://crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023401663.

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GLA变异分类对法布里病估计患病率的影响:筛选研究的系统回顾和荟萃分析

背景:法布里病(FD)的诊断与治疗具有重要意义。因此，明确GLA变异的致病性是至关重要的。本系统综述和荟萃分析旨在调查FD在高危人群和新生儿中的患病率，并评估不同GLA变体分类对FD估计患病率的影响。方法:于2023年2月21日检索EMBASE和PubMed数据库。观察性研究评估了FD的患病率，并报告了确定的GLA变异。使用美国医学遗传学和基因组学学院的标准和ClinVar数据库重新评估GLA变异的致病性。计算不同环境中FD的总患病率。该研究已在PROSPERO注册(CRD42023401663)，并遵循系统评价和荟萃分析指南的首选报告项目。结果:在纳入的3941项研究中，110项符合纳入标准。根据临床环境和致病性评估标准，FD的总患病率有显著差异。根据美国医学遗传学和基因组学学院的标准，左室肥厚/肥厚性心肌病患者的总患病率为1.2%(26项研究;10,080例筛查患者)，0.3%为终末期肾脏疾病/慢性肾脏疾病(38项研究;62,050名患者接受了筛查)，0.7%为卒中(25项研究;15,295例筛查患者)，0.7%的心脏传导障碍需要起搏器(3项研究;1033例患者筛查)，1.0%为小纤维神经病变(3项研究;904例患者筛查)，新生儿0.01%(15项研究;11 108 793名新生儿接受了筛查)。如果使用ClinVar数据库评估GLA变体，则总患病率不同，并且大多数在致病性分配上存在差异的患者携带以下变体中的一种:p.A143T, p.D313Y和p.E66Q。结论:本系统综述和荟萃分析描述了FD在新生儿和高危人群中的患病率，强调了在近期临床、生化和组织学数据背景下定期重新评估GLA变异的必要性。注册:网址:https://crd.york.ac.uk/PROSPERO/;唯一标识符:CRD42023401663。

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来源期刊

Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

9.20

自引率

5.40%

发文量

144

期刊介绍： Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.