Cornea verticillata supports a diagnosis of Fabry disease in non-classical phenotypes: results from the Dutch cohort and a systematic review. Issue 1 (12th February 2015)

• Record Type: Journal Article
• Authors: van der Tol, Linda; Sminia, Marije L; Hollak, Carla E M; Biegstraaten, Marieke
• Is Part Of: British journal of ophthalmology. Volume 100:Issue 1(2016)
• Page Start: 3
• Page End: 8
• Publication Date: 2015-02-12
• Subjects: Cornea -- Diagnostic tests/Investigation -- Epidemiology -- Genetics; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjophthalmol-2014-306433
• Languages: English
• ISSNs: 0007-1161

Abstract

Abstract : Background: 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. Methods: 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. Results: 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. Conclusions: 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.