Real-world clinical outcomes in adult patients with Fabry disease: A 20-year retrospective observational cohort study from a single centre

Abstract

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency, leading to the accumulation of globotriaosylceramide (Gb3) and progressive damage to the cardiovascular, renal, and cerebrovascular systems.

Aims: This study aimed to assess real-world clinical outcomes in FD patients, focusing on predominantly cardiovascular (CV), but also severe renal, and cerebrovascular outcomes, as well as CV and all-cause mortality. It also explored associations between age at diagnosis, Mainz Severity Score Index (MSSI), genetic mutations, and cardiometabolic risk factors such as smoking, hypertension, and obesity.

Methods: A retrospective observational cohort study of 405 patients with FD was conducted by reviewing medical records from a National Centre over a 20-year period. Clinical outcomes, predominantly cardiovascular, but also severe renal and cerebrovascular events and mortality were assessed. Age at diagnosis, MSSI, and cardiometabolic risk factors were also evaluated. Statistical comparisons were performed using the Mann-Whitney U test and Chi-square test, with significance set at p < 0.05.

Results: Nearly half (48 %) of patients experienced a defined clinical outcome. Higher age at diagnosis and baseline MSSI was observed in patients with poorer outcomes. The c.644 A > G (p.N215S) variant was linked with increased cardiovascular morbidity and mortality. Cardiometabolic risk factors such as smoking, hypertension, and obesity were common in patients with poorer outcomes. A high prevalence of arrhythmia, including paroxysmal atrial fibrillation (AF), was observed. Multi-morbidity was noted in deceased patients. Use of cardiometabolic therapies in at-risk groups (e.g. sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists) was low.

Conclusion: This study highlights the clinical burden of FD, particularly among males with the c.644 A > G (p.N215S) variant. The frequent presence of cardiometabolic risk factors in patients with adverse outcomes reinforces the importance of early diagnosis, comprehensive risk evaluation, and individualised management to improve long-term prognosis.

Keywords: Alpha-galactosidase; Atrial fibrillation; Cardiometabolic; Fabry disease; Mainz severity score index (MSSI).

Fig. 1

Flow diagram of patients included in the analysis.

Fig. 2

Age at diagnosis across study groups: Box and whisker chart comparing baseline age at diagnosis for groups: cardiac, renal, cerebrovascular, mortality, no outcome and all.

Fig. 3

Baseline median MSSI scores across groups: Box and whisker chart comparing baseline MSSI scores for groups: cardiac, renal, cerebrovascular, mortality, no outcome and all.

Fig. 4

Proportion of patients by outcome and risk factors: The X-axis represents the outcomes, while the Y-axis shows the number of patients as a percentage for each outcome and risk factor.

Fig. 5

Frequency of AF subtypes by gender: The X-axis represents the different subtypes, while the Y-axis indicates the number of patients. Data is split by male and female patients.