Assessment strategies in Fabry disease: insights from a multinational scoping review

Fabry disease (FD) is a rare X-linked lysosomal disorder caused by deficient α-galactosidase A (α-Gal A) activity. This scoping review synthesizes evidence on screening, diagnostic, and follow-up methods for FD.

We searched six databases for English and Spanish articles published from 2017 until April 2023. Eligible studies included human research on clinical manifestations and methods for screening, diagnosing, and monitoring FD, such as experimental and quasi-experimental studies, observational research, reviews, and guidelines. We followed PRISMA-ScR guidelines for screening and data extraction. We analyzed data with descriptive statistics and qualitative synthesis.

We included 383 studies, with cross-sectional designs being the most common (N:=155, 41%). Most studies were from high-income countries, and 199 (52%) did not report patients' phenotypes. Screening methods often combined clinical presentation, laboratory results, and imaging findings. Specifically, 14 studies (4%) focused on newborn screening. Clinical symptoms were described in 315 studies (82%) and were instrumental in diagnostic investigation. While hallmark manifestations were prevalent, less-recognized symptoms like tinnitus, early stroke, cerebrovascular dolichoectasia, conduction disorders, aortic root dilatation, and parapelvic cysts, were highlighted as important in clinical suspicion. Laboratory, particularly α-Gal A measurement (N.=183, 48%), and genetic sequencing were fundamental to diagnosis confirmation. Follow-up assessments concentrated on cardiovascular, genitourinary, and nervous systems, employing imaging and electrophysiological studies, along with various scales and questionnaires.

This review provides a comprehensive overview of screening, diagnostic, and monitoring strategies for FD, offering evidence-based insights to improve the clinical management of FD patients.