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.
