Fabry Disease: Pathogenesis, Clinical Symptoms, and Treatment with Enzyme Replacement Therapy

Abstract

Fabry disease is an X-linked lysosomal disorder caused by a deficiency in lysosomal glycohydrolase α-galactosidase A. This defect results in the accumulation of glycosphingolipids in various organ systems. Lipid deposits occur preferentially in vascular endothelial and smooth muscle cells, leading to vascular dysfunction, which results in tissue ischemia and vessel occlusion. Clinical symptoms are divided into two categories: early symptoms and late complications. Early symptoms include acroparesthesia, bouts of pain in the hands or feet, hypohidrosis, angiokeratoma, and gastrointestinal complications, which begin in the early childhood of patients with Fabry disease. Late complications include renal and cardiac dysfunction, and cerebral infarction, which determine morbidity and mortality after age 30 years. Enzyme replacement therapy (ERT) using recombinant human α-galactosidase A has recently developed, and has been shown to improve prognosis of patients with Fabry disease. Recent reports investigating long-term outcomes with ERT have shown that early initiation before the development of irreversible organ failure is particularly effective. Diagnosis at the early stage of the disorder and the early initiation of ERT alleviate symptoms and prevent late complications. The disorder should be widely recognized to improve patients' outcome.