Hereditary ATTR (hATTR) amyloidosis is passed down through families.
Hereditary ATTR amyloidosis is caused by a fault or mutation in the transthyretin (TTR) gene which is inherited (i.e. runs in families). The mutation results in an
abnormal TTR protein that is unstable and readily misfolds, forming aggregates which deposit as amyloid in various organs and tissues in the body. TTR is mostly made in the liver. Its role is to
transport the hormone thyroxine and retinol (Vitamin A) around the body, hence its name transthyretin.
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Symptoms of hereditary ATTR amyloidosis vary depending on the genetic variant, the organs that have been affected, and the extent to which the amyloid deposits have
caused damage. Symptoms can start at any time in adulthood. Common symptoms include:
Cardiomyopathy – Shortness of breath, palpitations and abnormal heart rhythm, ankle swelling (edema),
fainting, fatigue, chest pain (angina)
Peripheral neuropathy – Tingling and numbness in legs and feet, difficulty walking, limb weakness and
Autonomic neuropathy – Light-headedness when standing (orthostatic hypotension), bladder problems,
bowel problems, sexual dysfunction
Gastrointestinal – Decreased appetite, diarrhea, nausea, stomach pain, weight loss
Some ATTR variants are associated with specific symptoms. For example, the ATTR V30M variant typically
causes symptoms associated with peripheral neuropathy, whereas the ATTR V122I variant typically causes symptoms associated with cardiomyopathy. Most patients, however, will have symptoms
which indicate multiple organ involvement, regardless of what variant they have.