Monitoring disease progression in fabry disease: insights from a structured nominal expert consensus

Abstract Monitoring progression in Fabry disease is essential to optimize treatment and improve long-term outcomes. This work aimed to identify practical clinical indicators—or “alerts of progression”—to support timely therapeutic reassessment in patients receiving treatment. Using a nominal group technique, a panel of eight Spanish clinicians with expertise in Fabry disease established consensus-based criteria for disease monitoring across four domains: cardiac, renal, neurological, and disease-specific and treatment-related biomarkers. Candidate progression parameters identified through a preparatory evidence review and expert discussion were prioritized by allocating up to 5 points per expert within each domain. Parameters receiving ≥ 15% of the maximum available score within each domain were considered prioritized and were subsequently discussed by the panel. The prioritized parameters include decline in estimated glomerular filtration rate and increase in albuminuria, progression of ventricular hypertrophy or myocardial fibrosis, cerebrovascular events, worsening neuropathic pain, and elevation of lyso-GB3 in combination with neutralizing antibodies and clinical deterioration. These indicators were selected for their clinical relevance, measurability, and applicability across gender and phenotypes. The resulting framework provides a structured basis for detecting disease progression and guiding therapeutic reassessment, with the potential to harmonize monitoring practices and improve patient outcomes.