Abstract

FABRY DISEASE: AN EXPENSIVE ENZYME REPLACEMENT THERAPY

Pramod Singh Khatri*, Babra Javaid, Satyender Mathur, Sonam Pandey

Abstract

Fabry's is a destructive, progressive and life threatening disease which lessens survival of influenced individual. It is a genetic disorder of X linked inheritance caused by deficiency of lysosomal enzyme agalactosidase, resulting in accumulation of glycosphingolipids inside different body cells. Fabry's depositare characterized histopathologically as lamellate membrane like structure known as myeloid or Zebra bodies. Clinical indications of disease are hypohidrosis, acroparesthesias, heat intolerance, angiokeratomas, corneal opacities, cardiovascular arrhythmias, left ventricular hypertrophy, proteinuria and renal insufficiency. Diagnosis of Fabry's require a high clinical suspicion, physical investigation, organ specific tests and is affirmed by demonstrating low enzyme assay in homozygous males and gene typing in heterozygous females. Specific treatment for Fabry's disease is ERT with recombinant human a-galactosidase A. If the treatment is started early it has a promising role in renal and heart disease, however valuable role is still not characterized in CNS involvement. Management of Fabry disease consist of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, while dialysis or renal transplantation are accessible for patients encountering end-stage renal failure. With age, vital organ degrades, and at some point these organs might stop working. End-stage renal disease and life threatening cardiovascular complications limit life expectancy of untreated males (20 years) and females (10 years). While there is investigational proof that long term ERT can stop disease progression, the significance of adjunctive treatments ought to be accentuated and the possibility of developing an oral dose drives research forward into active site specific chaperones for effective treatment of Fabry disease.

Keywords: glycosphingolipids, hypohidrosis, acroparesthesias.