What is FAP?

Familial amyloid polyneuropathy (FAP) is a rare, inherited, and progressive disease caused by the buildup of amyloid fibrils made up of the protein transthyretin, which damage nerves and other tissues.

FAP is a form of transthyretin amyloidosis, also called ATTR amyloidosis, which is an umbrella term for conditions caused by the accumulation of transthyretin amyloid fibrils. FAP is a type of hereditary ATTR amyloidosis (commonly abbreviated hATTR or ATTRv amyloidosis), meaning that it is caused by genetic mutations that can be passed from parents to their biological children. In FAP, amyloid fibrils tend to accumulate in peripheral nerves — those found outside the brain and spinal cord — leading to nerve damage, or polyneuropathy.

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 is very rare in most other places throughout the world. It is estimated that 1 in 100,000 people have FAP in the U.S. and in most areas of Europe, though the specific disease incidence varies across different locations.

Causes of FAP

FAP is caused by the buildup of amyloid fibrils made of the transthyretin protein in different tissues and organs. Most commonly, FAP is caused by mutations in the TTR gene, which provides cells with instructions needed for making transthyretin. Mutations in the gene lead to the production of an abnormal transthyretin protein that clumps together, forming protein deposits that accumulate in several tissues, particularly in the nerves, heart, kidneys, and eyes. These deposits build up slowly and damage the affected organs, leading to the typical symptoms of the disease.

To date, more than 130 different mutations in the TTR gene have been reported, which may cause a variety of clinical symptoms. Some specific mutations appear to cause particularly severe disease, while others are associated with milder disease forms. Some people with mutations in the TTR gene experience no symptoms at all during their lifetime.

Disease-causing mutations associated with FAP are inherited in an autosomal dominant pattern, meaning that only one mutated copy of the gene is sufficient to trigger the disease. FAP equally affects both males and females.

While less common than mutations in the TTR gene, mutations in the genes APOA1 and GSN are associated with the abnormal protein buildup that occurs in FAP.

Symptoms of FAP

The age at which the first symptoms of FAP arise varies widely, with symptoms usually manifesting anytime between the ages of 20 and 80. Some people harboring disease-causing mutations may never experience any symptoms in their lifetime, though they may still pass these mutations to their children.

The hallmark symptoms of FAP include those associated with peripheral neuropathy, a condition resulting from peripheral nerve damage. Peripheral neuropathy commonly manifests as abnormal sensations in the hands and feet, such as numbness, tingling, or burning.

People with FAP may also experience symptoms of autonomic neuropathy, which occurs when the nerves that control involuntary bodily functions like blood pressure, breathing, and digestion, become damaged. Common symptoms of autonomic neuropathy include gastrointestinal and urinary problems, as well as erectile dysfunction.

Often, abnormal protein deposits build in the heart, damaging heart muscles. Heart failure is a common cause of death among people with FAP.

Depending on the extent of protein buildup across the body, other organs, such as the eyes and kidneys, may also be affected and possibly lead to blindness and kidney failure.

Diagnosis of FAP

The diagnosis of FAP is normally confirmed with a tissue biopsy — a procedure in which a small tissue sample is collected, processed, and examined for the presence of amyloid fibrils — and genetic testing to search for disease-causing mutations in the TTR gene.

Other medical assessments, ranging from tests designed to assess nerve and muscle function to those evaluating heart health, may also be useful in the diagnosis and management of FAP.

Treating FAP

There is currently no cure for FAP, but various treatments exist that can lessen symptom severity and disease burden.

In the U.S., Europe, and elsewhere, two medications are currently approved to treat FAP: Onpattro (patisiran) and Tegsedi (inotersen). Both work by lowering the production of transthyretin and helping to prevent the buildup of amyloid fibrils in tissues and organs. Clinical trials have demonstrated that these medications can ease FAP symptoms and improve patients’ quality of life.

Because transthyretin is mainly produced in the liver, a liver transplant may also be an option for some patients to lower the production of the defective protein. In patients with severe heart disease, a heart transplant may also be advised.

Physical therapy, or physiotherapy, can also help to improve patients’ ability to move, as well as ease pain and lower the risk of injuries. Occupational therapy can help patients find strategies to make their day-to-day lives easier to manage.

The search for better treatments is ongoing, with potential therapies designed to prevent or alleviate the accumulation of transthyretin aggregates, ease disease symptoms, and improve patients’ quality of life being investigated.


Last updated: June 11, 2021


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.