Familial transthyretin amyloidosis (FTA) is caused by changes (mutations) in the TTR gene. This gene is responsible for making a protein called transthyretin which transports vitamin A and a hormone called thyroxin to many parts of the body. Mutations in TTR lead to a transthyretin protein that is not made correctly. The faulty protein then folds up to form amyloid. Amyloid builds up in various parts of the body causing nerve and tissue damage.

Most people who have FTA have inherited the TTR mutation from a family member. However, a few people with FTA will have no family history of the disease and have a new (de novo) mutation in the TTR gene.

Familial transthyretin amyloidosis (FTA) is inherited in families in an autosomal dominant pattern. This means only one copy of a mutatedTTR gene is needed for a person to have the condition. The mutation can be inherited from a parent or can happen by chance for the first time (de novo) in an individual.

Each child of a person with FTA has a 50% chance of inheriting the mutation. Most children who inherit a TTR mutation will develop FTA, although they could be more or less severely affected than their parent. For reasons that are unclear, some people have mutations in the TTR gene and never develop FTA.

The exact incidence of familial transthyretin amyloidosis is unknown. It is more common in certain parts of Portugal, Sweden, and Japan. The common TTR gene mutation, known as Val30Met, associated with familial transthyretin amyloidosis (FTA) occurs in about 1 in 583 people in some parts of Portugal, compared to about 1 in 100,000 people in the US. A different TTR gene mutation associated with FTA, Val122Ile, is more common in parts of West Africa. While FTA is more common in certain parts of the world, it has been found across all ethnic groups and occurs equally in males and females.

Familial transthyretin amyloidosis (FTA) is a slowly progressing, adult-onset condition. Symptoms depend on which body parts are most affected. The age symptoms begin may also vary by country. In Portugal and Japan, people with FTA usually start developing symptoms in their late 20s to 40s. In other parts of the world, people with FTA may not have symptoms until after age 50.

The most common form of FTA affects the peripheral nervous system. The peripheral nerves send messages from the brain and spinal cord to the rest of the body. Other forms of FTA can affect the brain, spinal cord, heart, and eyes.

Symptoms of FTA include

• Weakness, numbness or pain in the lower legs and feet
• Carpal tunnel syndrome in both wrists
• Sexual impotence
• Urinary problems, protein in the urine
• Diarrhea or constipation
• Unexplained weight loss
• Dry eyes, increased pressure in the eyes (glaucoma), seeing ‘floaters’
• Abnormal heart beat, enlarged heart
• Getting dizzy when moving from sitting to standing (orthostatic hypotension)
• Dry eyes and mouth

Later symptoms may include muscle weakness and stiffness, difficulty with coordination, stroke, seizures, dementia, and congestive heart failure.

Less common symptoms include skin changes, hearing loss, shortness of breath, and anemia.

There is no treatment available for familial transthyretin amyloidosis (FTA) that reverses damage caused by amyloid deposits, but there are treatments that may prevent or delay progression. Treatment depends on which tissues are affected and how far the disease has progressed.

Liver transplantation is the "gold standard" for treatment for FTA, because it replaces the main source of amyloid. It may slow or halt progression of peripheral neuropathy, but the disease often still progresses in the eyes and brain. Transplantation ideally should be done as early as possible before there are severe neurological problems.

Several medications have been developed that slow the build-up of amyloid along nerves and in other parts of the body. These include tafamidis, diflunsial, and more recently inotersen and patisiran. There are other drugs that are currently under investigation for this condition.

Additional treatments may include heart and/or kidney transplantation, replacement of the liquid part of the eye (vitrectomy) for eye involvement, and carpal tunnel surgery.

Diuretics, medications that remove excess water and salt from the body, are often used to manage congestive heart failure associated with the disease. Other symptoms of FTA are treated as they arise.

The outlook and life expectancy for each person with familial transthyretin amyloidosis (FTA) varies and depends on the TTR genemutation present, organ(s) involved, and how early a person is diagnosed and treated. Some people whose symptoms begin at a younger age may live for only a few years after diagnosis, while older patients with slowly progressive disease can live for many years. On average, people with FTA typically live for 7-12 years after they are first diagnosed.

The long-term outlook after liver transplant is also influenced by many factors, including the type of amyloid present, nutritional status, age, and how much the brain and heart are involved. Newer medications are now available that help slow the build-up of amyloid and delay symptoms and it is not yet clear how these medications will affect the long-term outlook for people with FTA. People with questions about their personal outlook should speak with their healthcare providers.