What causes hereditary ATTR (hATTR) amyloidosis?
hATTR amyloidosis is caused by a gene change (mutation) that affects the function of a protein in the blood called transthyretin (TTR). This protein is made primarily in the liver.
- TTR, a naturally occurring protein made primarily in the liver, helps carry substances such as vitamin A.
- Gene mutations can lead to changes in the TTR protein that cause it to misfold (take on an abnormal shape).
- The change in shape causes the protein to gather and build up in the nervous (nerve), cardiac (heart), and gastrointestinal (digestive) systems. These gathered proteins are called amyloid fibrils. The amyloid fibrils build up and form deposits, which is what causes symptoms.
Amyloidosis refers to a group of conditions caused by the build-up of amyloid fibrils in the body. Each type is caused by a different misfolded protein. There are multiple types of amyloidosis, including amyloid A (AA) amyloidosis and amyloid light chain (AL) amyloidosis, which are the most common.
hATTR amyloidosis can cause a range of symptoms
The symptoms of hATTR amyloidosis can vary widely among people with the same mutation and even within families, though some do see a pattern of symptoms develop. Different symptoms may appear at different times for each individual. The age that initial symptoms appear may vary, ranging from the mid-20s to the mid-60s.
hATTR amyloidosis affects several parts of the body, including:
The peripheral nervous system, which is made up of nerves that branch out from the brain and spinal cord and communicate with the rest of the body including your arms and legs
- Polyneuropathy is caused by damage to the nerves of the peripheral nervous system, resulting in improper function
The cardiac system, which includes the heart and blood vessels, transports blood through veins and delivers oxygen to cells in the body
- Cardiomyopathy is a disease of the heart muscle that leads to heart failure
The autonomic nervous system, which is made up of nerves that connect the brain and spinal cord to organs such as the heart, stomach, and intestines, and helps to control bodily functions such as breathing, digestion, and heart rate
- Autonomic dysfunction occurs when the autonomic nervous system is not working correctly and may affect involuntary bodily functions
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