Fabry Disease in Asia: Insights from Taiwan’s Experience with Screening & Enzyme Therapy

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, which encodes α-galactosidase A (α-Gal A). The accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3) leads to progressive dysfunction of multiple organ systems, particularly the cardiac, renal, and neurological systems. The clinical course is highly heterogeneous and varies according to sex, residual enzyme activity, and the underlying genetic variant.

In Taiwan, the GLA variant c.640-801G>A (IVS4+919G>A) is relatively prevalent and is associated with a late-onset cardiac phenotype, typically presenting as left ventricular hypertrophy (LVH) during adulthood. Early treatment with enzyme replacement therapy (ERT) or pharmacological chaperone therapy can delay disease progression. However, the rarity of FD, its nonspecific clinical manifestations, and limited physician awareness often result in delayed diagnosis, leading to irreversible organ damage and reduced quality of life.

To facilitate earlier recognition and intervention, we developed and implemented an algorithm-based clinical decision support system (CDSS) within the computerized physician order entry (CPOE) system across the outpatient departments of three Taipei Medical University-affiliated hospitals. The algorithm incorporates clinical features that reflect the predominant cardiac phenotype observed in the Taiwanese population, including LVH, atrial fibrillation, and atrioventricular conduction block, together with other FD-associated manifestations such as impaired renal function and autonomic dysfunction.

During outpatient visits, the CDSS automatically reviews patients' electronic medical records in the background and generates alerts when individuals at high risk for FD are identified. Since its implementation in October 2024, the system has successfully identified patients at high risk for Fabry disease and facilitated timely confirmatory testing. This CDSS-driven approach provides a scalable model for proactive FD screening, enabling earlier diagnosis, timely family cascade screening, and prompt initiation of ERT before irreversible organ damage occurs.