[Fabry disease during the last 20 years: Analysis of a cohort of 107 patients, and focus on the F113L variant]

Abstract

Introduction: Fabry disease (FD, #OMIM 301 500) is an X-linked lysosomal disorder. Prior to the 2000s, it was considered a male-only disease. The emergence of two intravenous enzymotherapies (2001) and then of an oral chaperone molecule (2016) brought this rare disease into the spotlight. This work describes our cohort of patients with FD and aims to analyze the predominant classical and cardiac phenotypes (including the F113L variant).

Methods: In December 2022, we retrospectively analyzed all patients with FD managed within the lysosomal disease reference center. We describe and compare phenotypes before and after 2012.

Results: Our cohort included 107 patients (48 men-M, 59 women-F). The F113L variant accounted for 18% of cases, all in patients from Portugal. Before 2012, of the 45 patients followed (21M, 24F), 29 presented a classic form with acroparesthesia and cornea verticillata (64%) and 16 a predominantly cardiac form (36%), including 4 (1MH, 3F) with F113L variant. Eight patients died of cardiac complications (5M, 3F). After 2012, 62 new patients were included (27M, 35F), with 18 classic forms (29%) and 44 predominantly cardiac forms (71%). Of the 44 patients with a predominant cardiac form, 15 (9M, 6F) carried the F113L variant. Two men with the F113L allele had a severe form of the disease, requiring pacemaker implantation following cardiac arrest following complete atrioventricular block in one (aged 48), and registration for renal transplantation at age 64 in the other.

Conclusion: FD affects both men and women. The predominantly cardiac phenotype is now the most fequent. It is also observed in the majority of patients with the F113L variant. Extra-cardiac involvement is possible and should be investigated if this variant is detected.

Keywords: Cardiomyopathie hypertrophique; Diagnostic tardif; F113L; Fabry disease; Histoire naturelle; Hypertrophic cardiomyopathy; Late-onset; Maladie de Fabry; Natural history; Phenotype; Phénotype.