van der Tol Linda, Sminia Marije L, Hollak Carla E M, Biegstraaten Marieke
Department of Endocrinology and Metabolism, Amsterdam Lysosome Center 'Sphinx', Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Ophthalmology, Medical Center Alkmaar, Alkmaar, The Netherlands.
Br J Ophthalmol. 2016 Jan;100(1):3-8. doi: 10.1136/bjophthalmol-2014-306433. Epub 2015 Feb 12.
Screening for Fabry disease (FD) increasingly reveals individuals without characteristic features and with a variant of unknown significance in the α-galactosidase A (GLA) gene. Cornea verticillata (CV) assessment, as a characteristic sign of FD, may be a valuable diagnostic tool to assess whether these individuals have a non-classical phenotype or no FD at all.
We performed a systematic review to estimate the prevalence of CV in FD. Additionally, CV prevalence was assessed in the Dutch FD cohort. Data were stratified by gender and phenotype (classical, non-classical, uncertain, no-FD) using predefined criteria.
CV was assessed in 21 cohorts (n=753, 330 men, age 0-85 years). Pooled prevalence was 69% (74% men, 66% women). In six studies, 77 (19 men) individuals with a non-classical or uncertain diagnosis were identified. Individual data were available in 4/6 studies (n=66, 16 men). CV was present in 24% (n=16, 2 men). 101 (35 men) subjects from the Dutch cohort were grouped as classical, of whom 86% (94% men, 82% women including five women who used amiodarone) had CV. Of the 25 (11 men) non-classical patients, 4 (three men) had CV. Subjects in the uncertain and no-FD groups did not have CV.
CV is related to classical or biopsy-proven non-classical FD, with a very high sensitivity in classical men. Thus, presence of CV in an individual with an uncertain diagnosis of FD indicates a pathogenic GLA variant, in the absence of medication that may induce CV; if CV is absent, FD cannot be excluded.
法布里病(FD)筛查越来越多地发现一些没有典型特征且α - 半乳糖苷酶A(GLA)基因存在意义不明变异的个体。角膜涡状浑浊(CV)评估作为FD的特征性体征,可能是评估这些个体是否具有非典型表型或根本没有FD的有价值诊断工具。
我们进行了一项系统评价以估计FD中CV的患病率。此外,在荷兰FD队列中评估了CV患病率。使用预定义标准按性别和表型(经典型、非经典型、不确定型、无FD)对数据进行分层。
在21个队列(n = 753,330名男性,年龄0 - 85岁)中评估了CV。合并患病率为69%(男性74%,女性66%)。在六项研究中,确定了77名(19名男性)诊断为非经典型或不确定型的个体。4/6项研究(n = 66,16名男性)提供了个体数据。CV存在于24%(n = 16,2名男性)中。荷兰队列中的101名(35名男性)受试者被归类为经典型,其中86%(男性94%,女性82%,包括五名使用胺碘酮的女性)有CV。在25名(11名男性)非经典型患者中,4名(三名男性)有CV。不确定型和无FD组的受试者没有CV。
CV与经典型或经活检证实的非经典型FD相关,在经典型男性中敏感性非常高。因此,在FD诊断不确定的个体中,若不存在可能诱发CV的药物,CV的存在表明存在致病性GLA变异;若不存在CV,则不能排除FD。