Screening for Fabry disease in patients with left ventricular hypertrophy in China: A multicentre and prospective study

2024

ESC Heart Failure, Vol 11, Iss 6, Pp 4381-4389 (2024)

Abstract Aims Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH. Methods Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α‐galactosidase A (α‐Gal A) activity in males and both α‐Gal A and globotriaosylsphingosine (lyso‐Gb3) levels in females. Results The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8 ± 4.6 mm and an average age of 56.9 ± 17.2 years. In total, 43 patients (38 males, 5 females) exhibited low α‐Gal A activity measurement (1.1 ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P = 0.001), family history of HCM (37.5% vs. 2.3%, P T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post‐diagnosis identified an additional 14 confirmed cases. Conclusions This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso‐Gb3 and α‐Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

article

English

Wiley, 2024.

Fabry disease, left ventricular hypertrophy, dried blood spot, GLA mutations, enzyme replacement therapy, Diseases of the circulatory (Cardiovascular) system, RC666-701