Fabry disease is an X-linked lysosomal storage disorder in which cardiac involvement represents the leading cause of mortality. Despite continuous advances in diagnostic approaches, including genetic testing and cardiac imaging, delayed diagnosis and inappropriate management remain major clinical challenges, resulting in substantial impairment of quality of life and survival. Therefore, the establishment of a comprehensive, life-cycle management strategy encompassing screening, diagnosis, individualized treatment, and lifelong follow-up is essential to improve patient outcomes. In this review, we summarize recent advances in the epidemiology, genotype-phenotype correlations, diagnosis, and treatment of Fabry cardiomyopathy, and propose a novel concept for the life-cycle management of patients with Fabry cardiomyopathy.
Objective To explore the application value of echocardiography in the differential diagnosis of Fabry disease and hypertrophic cardiomyopathy (HCM). Methods Baseline data and echocardiographic parameters of Fabry disease patients and HCM patients admitted to the First Affiliated Hospital of Xi’an Jiaotong University between January 2022 and January 2024 were selected and compared between groups. The diagnostic ability for Fabry disease and HCM was analyzed using receiver operating characteristic curves and area under the curve (AUC). Results A total of 16 Fabry disease patients and 41 HCM patients were included. The Fabry disease group had lower age, body mass index, proportion of electrocardiogram abnormalities, and smoking history than the HCM group (P<0.05); the Fabry disease group had a longer medical history than the HCM group (P<0.05). The maximum thickness of the left ventricular myocardium and the ascending aortic diameter in the Fabry group were both smaller than those in the HCM group (P<0.05). The e-peak velocity in the Fabry group was greater than that in the HCM group (P<0.05). For the differential diagnosis of Fabry disease and HCM, the AUC for the e-peak velocity was 0.698 [95% confidence interval (0.502, 0.894), P<0.05], sensitivity was 41.7%, specificity was 100%, and Youden index was 41.7%. When the three factors were combined, both sensitivity and accuracy were significantly higher than the e-peak. The AUC was 0.773 [95% confidence interval (0.585, 0.961), P<0.05], with a sensitivity of 100% and specificity of 45.5%. There were no statistically significant differences in the 2D-speckle tracking imaging echocardiography parameters between the two groups, including global longitudinal strain of the left ventricle, strain of the apical segment, strain of the basal segment, and so on (P>0.05). Conclusion Echocardiography may have certain significance in the diagnosis of Fabry disease and HCM.
Objective To analyze the clinical phenotypic characteristics and plasma biomarker levels in female patients with Fabry disease (FD), and to explore their correlation with disease severity. Methods Clinical data were cross-sectionally collected between March and December 2024 from female FD patients who had previously been diagnosed across China. GLA gene mutations, α-galactosidase A (α-Gal A) activity, and plasma globotriaosylsphingosine (Lyso-GL-3) levels were measured. Disease severity was assessed using the Mainz Severity Score Index (MSSI). Spearman partial correlation analysis (controlling for age) was performed to evaluate correlations. Results A total of 21 female patients with FD from six pedigrees were enrolled. The disease severity of female FD patients varied considerably, with MSSI scores ranging from 2 to 31 [median (lower quartile, upper quartile): 11 (7, 24)]. Even within the same pedigree, organ involvement such as hearing loss and proteinuria was observed to occur earlier in some younger female patients than in their older female patients. Regarding biomarkers,13 patients (61.9%) had normal α-Gal A activity. All the 21 female patients had elevated Lyso-GL-3 levels (median: 15.24 nmol/L). After controlling for age, Lyso-GL-3 was positively correlated with MSSI score (rs=0.679, P=0.001) and left ventricular mass index (rs=0.486, P=0.030), and negatively correlated with α-Gal A activity (rs=?0.530, P=0.016). Estimated glomerular filtration rate showed no statistically significant correlation with any of the above parameters (P>0.05). Conclusions The disease severity of female patients with FD varies substantially. Significant phenotypic heterogeneity can also be observed among female heterozygotes with FD within the same pedigree. Plasma Lyso-GL-3 level is cross-sectionally correlated with disease severity and cardiac involvement, but its prognostic value requires validation in prospective studies.