Fabry disease: cardiac manifestations and therapeutic options.

: Fabry disease is a rare inherited lysosomal storage disorder caused by the partial or complete deficiency of the lysosomal enzyme alpha galactosidase A (alpha-Gal A), resulting in excess cellular glycosphingolipid deposition. Accumulation of the neutral glycosphingolipid globotriaosyl-ceramide predominates and involves small blood vessels, nerves, dorsal root ganglia, renal glomerular, and tubular epithelial cells and cardiomyocytes. Disease transmission is X-linked, therefore it predominantly affects males and females as asymptomatic carriers. However, females may also develop symptomatic disease of varying severity. Glycosphingolipid deposition in various tissues leads to episodic pain crises and acroparesthesias, gastrointestinal disturbances, angiokeratomas, corneal, and lenticular opacities, and eventually in the third to fifth decades of life, the kidney, heart and central nervous system are involved. Cardiac involvement is usually part of the multisystem disorder and presents in the fourth decade with other organ manifestations; however, a variant of Fabry disease with predominant cardiac manifestations has also been recognized. Patients may present with angina pectoris, dyspnea, palpitations, or syncope, and these symptoms are due to vascular, endothelial, myocardial (with increase in left ventricular mass), and conduction system involvement. Advanced cardiac disease may require a permanent pacemaker and cardiac transplant. Substrate inhibition with enzyme replacement therapy and gene therapy instituted early in the disease course might slow progression of the cardiac manifestations.