Amyloidosis, hereditary, transthyretin-related

Hereditary transthyretin amyloidosis is caused by changes (mutations) in the TTR gene. The TTR gene usually makes a protein. This protein moves other substances through the body, specifically vitamin A and thyroxine (a thyroid hormone). When proteins are made, they are "folded" into a specific shape. A mutation in the TTR gene causes transthyretin to be "misfolded" and abnormally shaped. The misfolded transthyretin proteins will clump together and form amyloid deposits. The abnormal transthyretin cannot perform its transporter job. In addition, the misfolded proteins start to build up in tissues and organs of the body. The misfolded proteins begin to merge together to form small or slender fibers called fibrils. When enough of the misfolded proteins (called amyloid) build up, they will damage the surrounding tissues and organs. The nerves, heart, kidneys, and gastrointestinal tract are commonly affected in people.

Amyloidosis may occur for reasons beyond genetics and gene changes (or mutations). Hereditary transthyretin amyloidosis is caused by mutations in the TTR gene. Several mutations have been found in the TTR gene. A specific mutation may be more likely to cause certain symptoms. Researchers have also learned that many genetic disorders are influenced by environmental factors and changes in other genes (called modifier genes). Scientists are trying to figure out how different changes in the TTR gene can lead to different forms of hereditary transthyretin amyloidosis and to determine whether anything else can influence how the disorder develops in a person.