Familial amyloid polyneuropathy

Familial amyloid polyneuropathy, also known as hereditary transthyretin amyloidosis or Corino de Andrade's disease, is an autosomal dominant neurodegenerative disease and a form of amyloidosis that chiefly damages the peripheral nervous system. It is caused by mutations in the TTR gene on chromosome 18, which encodes the protein transthyretin; the most common disease-causing change is a substitution known as Val30Met. Because the inheritance pattern is autosomal dominant, a person needs only one mutated copy of the gene to develop the disease. Symptoms typically begin between the ages of twenty and forty and include pain, abnormal sensation, muscular weakness, and disturbances of the autonomic nervous system, progressing over time into a broader polyneuropathy; in later stages the misfolded amyloid protein can also damage the kidneys and heart. Left untreated, the disease is invariably fatal within about a decade of onset, though liver transplantation, which removes the main source of mutant transthyretin, and newer pharmacological therapies now offer ways to slow or manage its progression. It was first identified in 1952 by the Portuguese neurologist Mário Corino da Costa Andrade.