Amyloidosis

Amyloidosis (Orphanet code 69, ICD-10 E85.0 corresponding to hereditary/familial amyloidosis) refers to a group of diseases characterized by the abnormal deposition of misfolded protein fibrils, called amyloid, in various organs and tissues throughout the body. In hereditary amyloidosis, the most common form is caused by mutations in the TTR gene (transthyretin amyloidosis, also known as familial amyloid polyneuropathy or familial amyloid cardiomyopathy). Other rarer hereditary forms involve mutations in genes encoding apolipoprotein A-I, apolipoprotein A-II, fibrinogen A alpha chain, lysozyme, or gelsolin. The amyloid deposits progressively disrupt normal organ structure and function, leading to multi-system disease. The body systems most commonly affected include the peripheral and autonomic nervous system, the heart, kidneys, gastrointestinal tract, and eyes. Key clinical features of hereditary transthyretin amyloidosis include progressive sensorimotor polyneuropathy (numbness, tingling, pain, and weakness starting in the feet), autonomic dysfunction (orthostatic hypotension, gastrointestinal dysmotility, erectile dysfunction), and restrictive cardiomyopathy leading to heart failure. Carpal tunnel syndrome is frequently an early manifestation. Renal involvement with proteinuria and progressive kidney failure is more prominent in fibrinogen or apolipoprotein-related forms. Vitreous opacities may occur in TTR amyloidosis. The treatment landscape for hereditary amyloidosis has evolved significantly. For TTR amyloidosis, disease-modifying therapies include TTR stabilizers (tafamidis, diflunisal) that prevent tetramer dissociation and fibril formation, and gene-silencing therapies (patisiran, inotersen, vutrisiran) that reduce hepatic TTR production. Liver transplantation was historically the standard treatment for familial amyloid polyneuropathy, as the liver is the primary source of circulating TTR. Heart transplantation or combined heart-liver transplantation may be considered in advanced cardiac amyloidosis. Supportive care addressing neuropathic pain, cardiac symptoms, and nutritional support remains essential. Early diagnosis and treatment initiation are critical, as organ damage from amyloid deposition is often irreversible.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Amyloidosis