Familial amyloid polyneuropathy (FAP) or transthyretin (TTR) amyloid polyneuropathy, is a rare, inherited, and progressive disease caused by the abnormal deposits of proteins or amyloids around peripheral nerves and other tissues.

FAP was first identified in 1952, when it was observed in several families in Portugal. In some areas of northern Portugal, FAP affects about 1 in 500 people, but it’s very rare in most countries throughout the world. It’s estimated that only 1 in 100,000 people have FAP in the U.S. and most areas of Europe. In other regions of the world, its incidence is a little higher.

Causes

FAP is caused by mutations in the TTR gene. To date, more than 100 different mutations in the gene have been reported, which may cause a variety of clinical symptoms; certain mutations appear to cause particularly severe disease and others, relatively mild disease. Some people with mutations in the TTR gene show no symptoms at all.

The TTR gene provides instructions for a protein, mainly produced in the liver, which is important for the proper transport of vitamin A and of a hormone called thyroxine throughout the body. The mutant TTR protein forms amyloid deposits in tissues, mainly in the nerves, heart, kidneys, and eyes, which build up slowly and cause damage to the affected organs, leading to symptoms of the disease.

The disease is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated TTR gene is sufficient to cause the disease. It is equally common in men and women.

Symptoms and diagnosis

The age at which the first symptoms of FAP develop varies widely and can appear between the ages of 20 and 80. As a result, some people with the disease may never experience any symptoms, but still may pass the defective gene to their children.

The symptoms of FAP include peripheral neuropathy that may appear early as an abnormal sensation in the legs and feet, such as numbness, tingling, or burning, and autonomic neuropathy, when the nerves that control involuntary bodily functions such as blood pressure, temperature control, and digestion, are damaged.

The disease usually worsens over five to 15 years and often ends with death from heart failure due to TTR protein deposits. Other symptoms depend on where protein accumulation occur in the body.

When doctors suspect FAP due to a patient’s symptoms, the diagnosis can be confirmed using a tissue biopsy (a small sample of tissue is processed and examined under a microscope) and genetic testing to search for mutations in the TTR gene.

Treatment

There is no cure for FAP, and the only available treatment consists of managing the symptoms of the disease. Physicians may prescribe TTR stabilizer drugs to slow the progression of the disease and reduce its impact on the patient’s daily life.

A liver transplant also may be an option for some patients with FAP to stop the production of the defective TTR protein. In patients with a severe heart disease, a heart transplant may be necessary.

The search for better treatments is ongoing, with different therapies designed to prevent or alleviate the accumulation of TTR proteins.

***

Note: FAP News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.