Fabry's disease

• We review Fabry's disease as a lysosomal glycosphingolipid storage disorder.
• We present the clinical manifestations and their pathophysiologic mechanisms.
• We present a recommendation for a diagnostic workup approach.
• We outline the different treatment modalities.
• We emphasize the recommendation for early treatment to prevent end organ failure.

Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the GLA gene, which leads to a deficiency in α-galactosidase A. The abnormal accumulation of glycosphingolipids, primarily globotriaosylceramide, manifests as serious and progressive impairment of renal and cardiac functions. In addition, patients experience pain, gastrointestinal disturbance, transient ischemic attacks and strokes. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. This review covers all basic aspects of the disease such as epidemiology, pathophysiology, clinical presentation by systems, diagnosis, management, prevention, and repercussions on quality of life. With the development of enzyme replacement therapy in the past few years, early initiation of treatment was found to be key for reduction of disease burden in major affected organs with improvement in neuropathic pain, decreased cardiac mass and stabilization of renal function, gastrointestinal symptoms, and hearing. This review aims to raise the awareness of the signs and symptoms of Fabry’s disease as well as to provide guidelines for the diagnosis and treatment.