Impact of enzyme replacement therapy on clinical manifestations in females with Fabry disease.

Abstract

Background: The aim of our multicenter study was to investigate the implementation of the European Fabry guidelines on therapeutic recommendations in female patients with Fabry disease (FD) and to analyze the impact of enzyme replacement therapy (ERT) in treated and untreated females.

Results: Data from 3 consecutive visits of 159 female FD patients from 6 Fabry centers were retrospectively analyzed. According to their treatment, patients were separated in 3 groups (untreated, n = 71; newly ERT-treated, n = 47; long-term ERT-treated, n = 41). Clinical presentation and laboratory data, including plasma globotriaosylsphingosine (lyso-Gb₃) levels were assessed. The observation time ranged from 49 to 62 months. ∼90% of female patients treated with ERT presented with at least one organ manifestation justifying treatment according to current European guidelines. Untreated females showed a less severe disease load with less FD-typical organ damage. All groups presented with a stable cardiac status (all p > 0.05) over time. ERT-treated females presented with a slight yearly loss of estimated glomerular filtration (eGFR) over time (both p < 0.05), which was comparable to the natural decline for this age. Plasma lyso-Gb₃ levels were higher in ERT-treated females and decreased by 0.95 [-4.44 to 4.08] ng/ml/year (p = 0.0002) in those who were newly ERT-treated.

Conclusions: Severely affected females with FD who were treated with ERT, and less severely affected untreated females, showed a broadly stable disease course over 5 years. The treatment decisions were largely based on the European guidelines for FD. In untreated females, it is crucial to explore if organ involvement is FD-related in order to make the correct treatment decision.