FROM NONSPECIFIC SYMPTOMS TO TIMELY DIAGNOSIS IN FABRY DISEASE: PRACTICAL STRATEGIES FOR EARLY DETECTION AND MANAGEMENT

Abstract

Fabry disease (FD) is an X-linked inherited disorder caused by α-galactosidase A deficiency (α-GalA), leading to accumulation of globotriaosylceramide and its metabolite globotriaosylsphingosine (Gb3/lyso-Gb3), with progressive damage primarily to the heart, kidneys, and nervous system. It presents as classic and late phenotypes, ranging from onset in childhood to adulthood, with great heterogeneity, especially in women. Multisystem manifestations include acroparesthesias, heat intolerance with hypo/anhidrosis, pain crises, and gastrointestinal complaints; characteristic signs are angiokeratomas and cornea verticillata. If untreated, progression to left ventricular hypertrophy, proteinuria/ chronic kidney disease (CKD), and cerebrovascular events is common. The diagnosis combines measurement of α-GalA activity (more informative in men), genetic testing (essential in women), lyso-Gb3 biomarkers and family screening. Specific treatment includes enzyme replacement therapy (ERT) and oral pharmacological chaperones for eligible variants, complemented by supportive, multidisciplinary care. Given the frequent diagnostic delay, early recognition of warning signs in primary and general care is critical to start therapy before irreversible damage, improving outcomes and quality of life. This brief narrative review synthesizes evidence on clinical presentation, practical diagnostic strategies, and current management, underscoring the importance of early clinical suspicion and family screening.