Fabry disease (FD) is a rare hereditary disorder caused by mutations in the gene encoding the enzyme alpha-galactosidase A. This enzyme deficiency results in the accumulation of glycosphingolipids in the organs, especially in the heart, which is often exhibited through left ventricular hypertrophy (LVH). Due to the overlapping symptoms with other conditions, FD is often misdiagnosed or diagnosed late, delaying appropriate treatment and increasing the risk of irreversible organ damage.
Considering the necessity to diagnose FD earlier, a new study investigates whether specific education of cardiologists can improve their awareness of the risk factors and diagnosis of FD, particularly when dealing with LVH patients, whose pathology has no explanation yet. The goal was to facilitate earlier diagnosis and timely treatment, potentially preventing irreversible complications.
This before-and-after, single-arm study was organized by Fondazione Policlinico A. Gemelli IRCCS in Rome, aimed to assess whether screening and diagnosis of FD among the cardiologists working in Italian hospitals without dedicated rare disease units. The study involved data on screening and diagnostics of FD over the last two years, as measured by participating cardiologists of different institutions to form a baseline. The educational intervention was organized as two phases: initially, three interactive online theoretical sessions concerning FD genetics, clinical manifestations, diagnostic approaches, imaging findings, treatment strategies, and distinguishing it compared to hypertrophic cardiomyopathy (HCM); second, five months of practical assistance through weekday video calls with an experienced practitioner to help in the decision-making process of the patient and the interpretation of ECG and echocardiographic studies.
Over a 12-month period (July 2023 to July 2024), the implementation included both proactive and retrospective evaluation of patients aged over 30 with unexplained left ventricular hypertrophy (LVH), LVH with ECG manifestations of Fabry cardiomyopathy, or LVH with coexisting chronic kidney disease, leukocytes, or a stroke or other systemic symptoms. Possible cases were subjected to dried blood spot (DBS) enzymatic testing and analysed by galactosidase alpha (GLA) gene sequencing upon receiving informed consent for genetic testing. The first result was that of evaluating the effect of the educational intervention, whether it significantly enhanced screening and diagnostic rates of FD when assessed by the Wilcoxon test (p < 0.05).
A center-based educational program concerning FD was undertaken by 15 Italian cardiologists working at various centers. They had done a total of 12 FD screening processes in the previous two years, on average 6 per year; they had discovered no new cases before the intervention. In the high-activity study time (July 2023 to July 2024), the screening reached the level of 45 screens (p = 0.018), representing an 8-fold increase. The average age of the patients was 61 years, with 82% males. Most of these individuals had unexplained LVH (n = 43), two of them showed slightly thickened walls and characteristic patterns of cardiac MRI. Chronic kidney disease and hypertension were found in 36% and 40%, respectively.
A total of 4 new index FD cases were diagnosed, including two men and two women, with a diagnostic positivity rate of 8.8%. Each was immediately referred to treatment, and family screening resulted in further diagnoses. These results indicate that focused education would go a long way in enhancing the ability to detect FD and manage them clinically in cardiology.
This study clearly demonstrated that targeted education and mentorship significantly improved FD screening and diagnosis in the cardiology setting. The intervention was more effective than standard practices, enabling earlier detection and initiation of treatment before irreversible organ damage occurred. In conclusion, enhancing clinician awareness, especially in the context of unexplained LVH, can play a critical role in improving outcomes for patients with FD and their families.
References: Meucci MC, Lillo R, Calcagnino M, et al. How to Enhance Diagnosis in Fabry Disease: The Power of Information. Cardiogenetics. 2025;15(3):21. doi:10.3390/cardiogenetics15030021
