ATTR-PN, or transthyretin amyloid polyneuropathy, is a rare form of hereditary ATTR (hATTR) amyloidosis, also known as familial amyloidosis. This condition happens when mutations (changes) in the transthyretin (TTR) gene cause abnormal protein to build up in the body. People living with ATTR-PN may experience nerve-related (neurologic), digestive (gastrointestinal), and heart-related (cardiovascular) symptoms — often severe enough to impact daily life.

Although rare, health experts estimate that around 10,000 to 40,000 people worldwide are living with ATTR-PN. Symptoms usually begin either around age 30 or after age 50, depending on the specific genetic variant.

ATTR-PN falls under the umbrella of a disease called amyloidosis. In amyloidosis, proteins in the body fold incorrectly, forming sticky clumps called amyloid fibrils. These fibrils build up in tissues and organs, interfering with how they function.

ATTR-PN is extremely rare, with only around 10,000 to 40,000 people worldwide living with it.

Living with a rare disease like ATTR-PN can be overwhelming. You might not have heard of it before, and you may not know what to expect. Here are six important facts to help you better understand ATTR-PN — including what causes it, how it’s diagnosed, what symptoms to look for, and the treatment options available.

1. The Cause of ATTR-PN Is Genetic

ATTR-PN is a hereditary disease caused by a mutation (change) in the transthyretin gene. This mutation leads to the misfolding of TTR proteins. These abnormally shaped proteins collect to form amyloid fibrils, or fibers, which are deposited in organs and tissues, where they can cause damage.

When amyloid fibers accumulate around the peripheral nerves, it’s known as transthyretin amyloid polyneuropathy.

2. The Symptoms of ATTR-PN Vary and Are Nonspecific

ATTR-PN tends to affect sensory, motor, and autonomic nervous systems — including functions you don’t consciously control, like digestion, blood pressure, and body temperature. Because of this, people who have the disease often experience a range of symptoms, such as:

• Burning sensations
• Cold skin
• Constipation
• Depression
• Diarrhea
• Digestive system blockages
• Dizziness/fainting
• Fatigue
• Frequent vomiting
• Heightened sensitivity to touch
• Insomnia
• Loss of appetite
• Mood changes
• Muscle weakness and pain
• Numbness/lack of sensitivity
• Sexual dysfunction
• Sudden drops in blood pressure
• Upset stomach
• Urinary incontinence
• Vision and hearing problems

Symptoms related to ATTR-PN are usually vague, meaning they could be signs of something other than the disease. This can contribute to delays in diagnosis.

Symptoms related to ATTR-PN are usually vague, meaning they could be signs of something other than the disease. This can contribute to delays in diagnosis, as can a lack of awareness of the condition itself.

3. Diagnosing ATTR-PN Is a Complex Process

Diagnosing ATTR-PN typically involves two steps:

• A thorough medical history
• A comprehensive neurological exam that examines factors like gait (walking pattern), balance, and motor function

If neither of these steps rules out ATTR-PN, a doctor — generally a neurologist — will perform further tests to confirm the diagnosis.

These tests include:

• A biopsy to confirm if amyloid fibril deposits are present — You made need a biopsy taken from more than one area of the body
• An evaluation of the specific type of amyloid fibril deposits found during a biopsy (if any)
• Genetic testing to determine if you have a TTR gene mutation

Diagnosing ATTR-PN often requires collaboration between neurologists, cardiologists, and geneticists. ATTR-PN can affect multiple systems in the body, monitoring spread to organs such as the heart, kidneys, and eyes is also important.

Detecting and treating ATTR-PN early is critical to preventing organ damage, which could be permanent.

4. Treatments for ATTR-PN Help Slow Its Progression

The original treatment for ATTR-PN was liver transplantation. That’s because the liver produces most of the TTR protein. Although liver transplant remains a treatment option for people with ATTR-PN, some of its limitations are now better understood, including that it’s more effective in treating cases caused by certain types of genetic mutations.

Researchers have also developed new drugs to treat the disease that don’t require a major surgical procedure. These medications focus on preventing or slowing down disease progression. That means stopping amyloid fibrils from forming or collecting around the peripheral nerves.

Some medications have been approved by the U.S. Food and Drug Administration (FDA) to treat ATTR-PN. Others are used off-label, meaning they’re approved for a different condition but have been shown to be effective for ATTR-PN.

FDA-approved drugs for ATTR-PN include:

• Eplontersen (Wainua)
• Inotersen (Tegsedi)
• Patisiran (Onpattro)
• Vutrisiran (Amvuttra)

These drugs are known as gene silencers. They recognize and block the instructions for making TTR proteins — as a result, your cells no longer make them.

Examples of off-label treatments include:

• Diflunisal — A nonsteroidal anti-inflammatory drug keeps TTR proteins from folding improperly
• Tafamidis (Vyndaqel, Vyndamax) — FDA-approved for ATTR cardiomyopathy (ATTR-CM, a type of amyloidosis affecting the heart)

Supportive Therapies for ATTR-PN

Because ATTR-PN affects motor function, doctors may recommend supportive therapies to help reduce symptoms and improve quality of life.

For example, occupational therapy can help improve quality of life by making activities of daily living — like eating, bathing, and dressing — easier. Physical therapy can help improve strength and reduce pain in the bones and joints.

5. ATTR-PN Outlook Improving Thanks to New Therapies

Life expectancy for hereditary transthyretin amyloidosis depends on a variety of factors, including:

• Specific gene mutation that’s present
• Age at diagnosis
• Whether amyloid deposits have led to cardiomyopathy — This condition causes the heart muscle to stiffen and not work as well.

Without treatment, hATTR advances quickly. A 2021 study found that untreated hATTR amyloidosis had a median survival rate of 4.7 years after diagnosis.

ATTR-PN usually progresses in three stages:

• Stage 1 — Loss of sensory function in the feet that moves up to the legs and, eventually, to the hands
• Stage 2 — Increasing loss of mobility, with people often needing walking aids within three to five years
• Stage 3 — Significant loss of mobility, with people typically requiring a wheelchair 10 years after disease onset

For some people with early-stage (appearing around age 30) ATTR-PN and a Val30Met mutation, the expected survival rate is about 12 years after disease onset. For others with late-onset (appearing at or after age 50) ATTR-PN, the median survival is seven years.

Therapies like liver transplantation and medications can help slow the progression of the disease and improve survival in the early stages.

6. Support Helps Improve Life With ATTR-PN

Despite improvements in diagnosing and treating ATTR-PN, people with the disease can still face challenging and frustrating paths. MyAmyloidosisTeam members share challenges with symptoms, getting appointments with neurologists, and affording their treatments:

• “My neuropathy pain and weakness is making life difficult.”
• “Make your appointments right away. I had to wait three months.”
• “Finally received approval of my treatment through Healthwell Foundation. How long does it take to improve polyneuropathy?”

Support groups, like MyAmyloidosisTeam, are an important resource for both people living with the disease and their family members as they navigate this rare disease. “I’m glad to finally have people to talk to who understand and can relate to my symptoms,” one member shared.

Connect With Others Who Understand

MyAmyloidosisTeam is the social media network for people with amyloidosis and their loved ones. It brings more than 2,500 members together to ask questions, give advice, and share their experiences with others who understand what they’re going through.

Are you living with transthyretin amyloid polyneuropathy, or ATTR-PN? Share your experience in the comments below, or start a conversation by posting on your Activities page.