Fabry Disease: A Review

Abstract

Fabry disease (FD) is a X-linked lysosomal storage disorder caused by pathogenic variants in GLA. Deficiency of an enzyme leads to the buildup of glycosphingolipids in various cell types, including vascular endothelial cells, podocytes, cardiomyocytes, neurons and others. Symptoms like hypohidrosis, neuropathic pain, hypertrophic cardiomyopathy, angiokeratomas, arrhythmias and progressive chronic kidney disease (CKD) to end-stage renal disease (ESRD) were considered as organ manifestations. Early diagnosis enables disease modifying therapy that can prevent or slow organ damage. This review article mainly focusses on genotype-phenotype spectrum, molecular pathology & diagnostic biomarkers, diagnostic approach & screening recommendations, treatment & established therapies, supportive & organ-directed care, treatment evidence & outcomes, special diagnostic & management issues, newborn & popular screening challenges, bio-markers use in monitoring & treatment decisions, safety & adverse effects of the treatment, gaps in evidence & research priorities and practical clinical recommendations of FD. In male with early CKD or cryptogenic stroke, with neuropathic pain, corneal verticillata, angiokeratomas or with un-explained LV hypertrophy FD is suspected, so the tests must be done promptly. Diagnostic algorithm for both males and females must be monitored. In males, ?-galactosidase A activity must be measured and GLA genetic testing must be performed, whereas, in case of females, GLA genetic test must be performed regardless of enzyme level and measure plasma lyso-Gb3 for baseline monitoring. After multi-disciplinary evaluation patients who were diagnosed with ERT or Migalastat for amenable mutations must be initiated to disease-modifying therapy at earliest. Cardiac, neurological status and renal activities must be monitored regularly. With promising results emerging gene-therapies and substrate reduction strategies can be helpful in treating yet, long term evaluation is required. Vigorous genotype interpretation, multi-disciplinary care and careful counseling must be considered as critical clinical priorities.