Transthyretin-associated neuropathic amyloidosis: Pathogenesis and treatment

摘要: Hereditary amyloidoses form a clinically and genetically heterogeneous group of autosomal dominantly inherited diseases characterized by the deposit insoluble protein fibrils in extracellular matrix. They typically present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, cardiomyopathy gastrointestinal features, occasionally accompanied vitreous opacities renal insufficiency. Other phenotypes are nephropathy, gastric ulcers, cranial nerve dysfunction, corneal lattice dystrophy. Rarely, involvement leptomeningeal or cerebral structures dominates clinical picture. The age at onset is as early 17 late 78 years. basic constituents amyloid fibers physiologic proteins that have become amyloidogenic through determined conformation changes. Mutated transthyretin (TTR), formerly termed prealbumin, most frequent offender hereditary amyloidosis. Orthotopic liver transplantation (OLT) stops progression disease, which otherwise invariably fatal, removing main production site protein. indications for OLT its success depend on grade cardiovascular dysfunction time surgery, age, comorbidity, type mutation. Alternative treatment modalities drugs stabilizing native tetrameric TTR inhibiting fibril formation currently being studied.