# Fabry Disease Screening in Patients with Idiopathic HCM or LVH: Data from the Multicentric Nationwide F-CHECK Study

## TL;DR

This study found that 3.4% of Portuguese patients with unexplained heart conditions had Fabry disease, emphasizing the need for broader screening.

## Contribution

The study reports a significant prevalence of Fabry disease in a Portuguese cohort with unexplained cardiomyopathies and identifies new clinical indicators for screening.

## Key findings

- Fabry disease was diagnosed in 14 out of 409 patients (3.4%) with unexplained cardiomyopathy.
- FD was associated with systemic symptoms like acroparesthesias and a higher risk of arrhythmic events and cerebrovascular disease.
- Most FD cases involved non-founder GLA gene mutations that were still clinically significant.

## Abstract

Background/Objectives: Fabry disease (FD) is a rare X-linked disease caused by the deficient activity of the enzyme α-galactosidase A. Cardiac involvement is particularly critical, often determining the disease prognosis. Epidemiological data on FD in Portugal are limited and inconsistent, highlighting the need for targeted screening. The F-CHECK study aimed to determine the prevalence of FD through the systematic screening of a Portuguese cohort of patients with unexplained cardiomyopathies. Methods: This multicenter observational study (NCT05409846) assessed the prevalence and clinical characteristics of FD in a Portuguese cohort (n = 409) of patients from 10 central hospitals who presented with unexplained cardiomyopathies, including idiopathic hypertrophic cardiomyopathy (HCM), left ventricular hypertrophy, dilated-phase HCM, and dilated cardiomyopathy with late gadolinium enhancement in the inferolateral segment. Screening was performed using dried blood spot assays to measure α-galactosidase A activity and/or by GLA gene sequencing in whole-blood samples. Results: FD was diagnosed in 14 patients, corresponding to a prevalence of 3.4%. FD diagnosis was significantly associated with systemic manifestations such as acroparesthesias (p = 0.027) and angiokeratomas (p = 0.003), as well as an increased risk of prior arrhythmic events (p = 0.021) and cerebrovascular disease (p = 0.016). Most FD patients (57%) presented a non-founder mutation in the GLA gene; however, they were pathogenically relevant. Conclusions: The observed 3.4% prevalence highlights the importance of systematic FD screening among Portuguese patients with unexplained cardiomyopathy, extending beyond classic hypertrophic presentations to dilated forms. Specific clinical signs, electrocardiogram findings, and cardiac imaging features can serve as valuable indicators to guide targeted genetic testing for FD.