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Cornea verticillata supports a diagnosis of Fabry disease in non-classical phenotypes: results from the Dutch cohort and a systematic review
  1. Linda van der Tol1,
  2. Marije L Sminia2,3,
  3. Carla E M Hollak1,
  4. Marieke Biegstraaten1
  1. 1Department of Endocrinology and Metabolism, Amsterdam Lysosome Center ‘Sphinx’, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Ophthalmology, Medical Center Alkmaar, Alkmaar, The Netherlands
  1. Correspondence to Dr Marieke Biegstraaten, Academic Medical Center, Department of Internal Medicine, Room F5-166, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; M.Biegstraaten{at}amc.uva.nl

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.

  • Cornea
  • Diagnostic tests/Investigation
  • Epidemiology
  • Genetics

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