Familial Amyloid Polyneuropathy
An inherited disease of nerve-damaging protein deposits
Quick Facts
- Type: Inherited multisystem nerve disorder
- Cause: Genetic change, often in the TTR gene
- Affects: Peripheral and autonomic nerves, often the heart
- Course: Progressive; treatments can slow it
Overview
Familial amyloid polyneuropathy (FAP) is an inherited condition in which an abnormal, misfolded protein clumps together and deposits in body tissues as a substance called amyloid. These deposits build up in the peripheral nerves and often in the heart, digestive tract, and other organs, gradually interfering with their function. In the nerves, this causes a progressive polyneuropathy, meaning damage to many nerves at once.
The most common form is caused by a change in the gene for a protein called transthyretin (TTR). Because it is inherited, the condition can run in families. FAP typically progresses over years, affecting both the sensory and motor nerves and the autonomic nerves that control automatic body functions. While it has historically been a serious, progressive disease, newer treatments can now slow its course.
Symptoms
Symptoms usually begin in adulthood and reflect damage to several types of nerves and organs.
- Numbness, tingling, and pain starting in the feet and progressing upward
- Weakness and loss of muscle, leading to difficulty walking
- Autonomic symptoms such as dizziness on standing, constipation or diarrhea, and bladder or sexual problems
- Unintended weight loss
- Heart symptoms, including palpitations, shortness of breath, and swelling, when the heart is involved
- Carpal tunnel symptoms in the hands, sometimes an early sign
Because the disease can affect the heart, new breathlessness, fainting, or significant swelling should be evaluated promptly.
Causes
FAP is caused by an inherited genetic change that leads to the production of an unstable protein.
- TTR gene change: The most common cause, producing an unstable transthyretin protein that misfolds and forms amyloid deposits.
- Amyloid deposition: The deposits accumulate in nerves and organs over time, disrupting their structure and function.
- Other rare gene changes: A few other inherited proteins can cause similar amyloid neuropathies.
It is usually inherited in an autosomal dominant pattern, meaning one affected parent can pass the gene change to a child. Not everyone who inherits the change develops symptoms at the same age or to the same degree.
Risk Factors
- A parent or close relative with FAP or hereditary amyloidosis
- Carrying a disease-causing change in the TTR or related gene
- Ancestry from regions where certain TTR variants are more common
- Adult age, when symptoms typically emerge
Diagnosis
Diagnosis can be challenging because symptoms overlap with other neuropathies, so a high index of suspicion and specific tests are important.
- Genetic testing: Identifies the TTR or other gene change and confirms the inherited form.
- Nerve conduction studies and EMG: Document the polyneuropathy.
- Tissue biopsy: A sample stained for amyloid can confirm the deposits.
- Heart tests: Echocardiography, cardiac MRI, and specialized scans assess heart involvement.
Treatment
Treatment aims to slow the buildup of amyloid and manage symptoms and organ involvement. Care is usually coordinated by specialists.
- Disease-modifying therapies: Newer medicines can stabilize the transthyretin protein or reduce its production, slowing disease progression.
- Liver transplantation: Historically used in some cases because the liver makes most transthyretin.
- Symptom management: Treatments for nerve pain, blood pressure swings, and digestive and bladder symptoms.
- Heart care: Management of heart involvement when present.
Outcomes are best when the disease is recognized and treated early, before extensive nerve and organ damage occurs.
Living With the Condition
- The disease cannot be prevented, but genetic counseling helps families understand inheritance and testing options
- Early diagnosis allows disease-slowing treatment to begin sooner
- Relatives of affected people may consider genetic testing and monitoring
- Regular specialist follow-up tracks nerve and heart involvement
- Supportive therapies help maintain mobility and manage symptoms
When to See a Doctor
See a doctor for progressive numbness, weakness, or autonomic symptoms, especially if a relative has had a similar nerve or heart condition. Seek prompt care if you develop:
- New or worsening shortness of breath, palpitations, or fainting
- Significant swelling in the legs or abdomen
- Rapidly worsening weakness or difficulty walking
Because FAP can affect the heart, these symptoms deserve timely evaluation.
Frequently Asked Questions
What is familial amyloid polyneuropathy?
It is an inherited disease in which an abnormal protein misfolds and builds up in tissues as amyloid, damaging the peripheral and autonomic nerves and often the heart. The most common form is caused by a change in the transthyretin (TTR) gene.
How is FAP inherited?
It is usually passed down in an autosomal dominant pattern, meaning one affected parent can pass the gene change to each child. Not everyone who inherits the change develops symptoms at the same age or severity, so genetic counseling is helpful for families.
What are the early symptoms?
Early symptoms often include numbness, tingling, and pain in the feet, sometimes with carpal tunnel symptoms in the hands. Autonomic problems such as dizziness on standing and bowel changes can also appear early, along with unexplained weight loss.
Can familial amyloid polyneuropathy be treated?
Yes. Newer disease-modifying medicines can stabilize the transthyretin protein or reduce its production, slowing the disease. Symptom management and heart care are also important. Outcomes are best when treatment starts early.
Does FAP affect the heart?
It often does. Amyloid can deposit in the heart muscle, causing palpitations, shortness of breath, and swelling. Because of this, new heart symptoms in someone with FAP should be evaluated promptly, and the heart is monitored over time.
References
- National Institute of Neurological Disorders and Stroke (NINDS). Peripheral Neuropathy.
- Amyloidosis Foundation. Hereditary (familial) amyloidosis.
- MedlinePlus, U.S. National Library of Medicine. Transthyretin amyloidosis.
- National Library of Medicine. StatPearls: Familial Amyloid Polyneuropathy.