2.1. Transthyretin amyloidosis

More than 100 mutations in the TTR gene have been found to cause transthyretin amyloidosis. Nearly all of these mutations change one protein building block (amino acid) in the transthyretin protein. The most common mutation found in people with transthyretin amyloidosis replaces the amino acid valine with the amino acid methionine at position 30 in the transthyretin protein (written as Val30Met or V30M). This mutation is seen most commonly in the Portuguese and Swedish populations, although it is found in affected people worldwide. Another common mutation replaces the amino acid valine with the amino acid isoleucine at position 122 in the transthyretin protein (written as Val122Ile or V122I). It is estimated that 3 percent to 3.9 percent of African Americans and 5 percent of some West African populations have this mutation.

Most of the TTR gene mutations that cause transthyretin amyloidosis are thought to alter the structure of transthyretin, impairing its ability to bind to other transthyretin proteins and altering its normal function.

2.2. Carpal tunnel syndrome

2.3. Other disorders

In older adults, deposits of transthyretin protein cause a condition called senile systemic amyloidosis. People with this condition do not have a mutation in the TTR gene; for reasons that are unclear, the transthyretin protein abnormally begins to form protein deposits. The most common place for amyloidosis in people with this condition is the heart, causing slowly progressive heart failure. Other sites of amyloidosis may include the lungs, blood vessels, and kidneys. It is estimated that 10 percent to 25 percent of people older than 80 have senile systemic amyloidosis.