ATTR amyloidosis as a unique autonomic disorder

Abstract

Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) is a hereditary systemic amyloidosis caused by mutations in the TTR gene. It is characterized by systemic accumulation of amyloid fibrils in small fiber nerves and autonomic system. Patients with ATTR-FAP frequently experience multiple autonomic dysfunction symptoms, such as orthostatic hypotension, anhidrosis, gastrointestinal motility disorder, and sexual impotence at the early stage. The management of autonomic dysfunction affects prognosis and the quality of life of the patient. Recently, to evaluate small fiber neuropathy, Sudoscan is a useful tool as noninvasive method in addition to skin biopthy. More recently, a novel disease-modifying therapeutic drug for ATTR-FAP, stabilizers of the tetrameric TTR, has been approved and gene silencing therapies are now under clinical trials. These drugs are thought to be more effective in the early stage; hence, effective of those drugs on autonomic dysfunction is expected.