Transthyretin familial amyloid polyneuropathy

Transthyretin familial amyloid polyneuropathy is a rare, life-threatening, autosomal dominant hereditary disorder caused by pathogenic mutations in the transthyretin (*TTR*) gene Pathophysiologically, the genetic variant destabilizes the hepatic transthyretin tetramer, causing misfolded protein monomers to aggregate and deposit extracellularly as insoluble amyloid fibrils within the endoneurium and other tissues Clinically, it is characterized by a progressive, length-dependent sensorimotor poly...

Transthyretin familial amyloid polyneuropathy is a rare, life-threatening, autosomal dominant hereditary disorder caused by pathogenic mutations in the transthyretin (*TTR*) gene It primarily affects the peripheral and autonomic nervous systems of adults, frequently involving the cardiovascular system and other organs Clinically, it is characterized by a progressive, length-dependent sensorimotor polyneuropathy—typically starting with small-fiber sensory deficits and weakness in the lower extrem...

It primarily affects the peripheral and autonomic nervous systems of adults, frequently involving the cardiovascular system and other organs

Pathophysiologically, the genetic variant destabilizes the hepatic transthyretin tetramer, causing misfolded protein monomers to aggregate and deposit extracellularly as insoluble amyloid fibrils within the endoneurium and other tissues

Clinically, it is characterized by a progressive, length-dependent sensorimotor polyneuropathy—typically starting with small-fiber sensory deficits and weakness in the lower extremities—accompanied by severe dysautonomia, such as gastrointestinal dysmotility and orthostatic hypotension