A Randomized Controlled Trial

FABRY DISEASE IS A RARE X-LINKED recessive glycosphingolipid storage disorder that is caused by a deficiency of the lysosomal enzyme a-gal A (a-galactosidase A). Its incidence has been estimated to be 1:117 000 births. Globotriaosylceramide (Gb3), the glycosphingolipid substrate of this enzyme, accumulates within vulnerable cells, tissues, and organs of affected patients. Affected cell types include endothelial cells, pericytes, smooth muscle cells of the vascular system, renal epithelial cells, myocardial cells, and dorsal root ganglia neuronal cells. Clinical onset of the disease typically occurs during childhood or adolescence with recurrent episodes of severe, debilitating neuropathic pain in the extremities. The neuropathic pain syndrome is thought to be secondary to a small-fiber peripheral neuropathy caused by destruction of dorsal root ganglion cells by progressive deposition of Gb3. With increasing age, Gb3 progressively accumulates throughout the body. Deposition of Gb3 occurs within multiple sites throughout the nephrons and renal vasculature. Progressive glomerular injury is associated with mesangial widening and ultimately with segmental and global glomerulosclerosis. Patients often also develop hypertrophic cardiomyopathy, coronary artery disease, valvular abnormalities, dysrhythmias, and conduction disturbances. Death usually occurs during the fourth or fifth decade of life secondary to renal, cardiac, or cerebrovascular complications. To date, there has been no definitive therapy for Fabry disease. Previous studies have demonstrated that partially purified prepara-