Abstract

AN INTEGRATIVE REVIEW ON FABRY DISEASE: FROM ITS MOLECULAR MECHANISM TO MODERN THERAPIES

Ms. P. Devika*, Ms. D. Jayashree, Ms. S. Sapna Banu, Mrs. S. Sathiya Priya, Ms. T. Yathika, Ms. A. Mumtaj Begum*

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder caused by pathogenic mutations in the GLA gene, resulting in deficient activity of the enzyme α-galactosidase A. Reduced enzymatic function leads to progressive intracellular accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its deacylated metabolite lyso-Gb3, which disrupt cellular homeostasis and promote multisystem involvement. The disease predominantly affects the kidneys, heart, nervous system, and vascular endothelium, contributing to significant morbidity and reduced life expectancy. Advances in diagnostic strategies, including enzyme activity assays, molecular genetic testing, and biomarker assessment, have improved early disease identification and clinical monitoring. Current therapeutic approaches, such as enzyme replacement therapy, pharmacological chaperone therapy, substrate reduction strategies, and emerging gene-based interventions, aim to correct the underlying metabolic defect. However, treatment effectiveness is frequently limited by immune-mediated reactions, short biological half-life, and inadequate penetration across the blood–brain barrier. Recent progress in nanotechnology-based drug delivery systems has demonstrated potential to enhance therapeutic stability, tissue targeting, and overall clinical efficacy. This review provides a comprehensive overview of Fabry disease pathogenesis, diagnostic developments, and evolving treatment strategies, highlighting future directions toward improved, personalized, and more durable disease management approaches.

Keywords: Anderson‑Fabry Disease, GLA gene mutation, alpha-galactosidase A deficiency, globotriaosylceramide (Gb3) accumulation, lyso-Gb3 biomarker, X-linked lysosomal storage disorder, endothelial dysfunction.