Amyloidosis Symptoms and Side Effects/Physical Symptoms and Side Effects

Muscle Weakness in Polyneuropathy: What To Expect

Medically reviewed by Kiran Chaudhari, M.B.B.S., M.D., Ph.D.

Written by Carrie Madormo, RN, MPH

Posted on August 31, 2026

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Key Takeaways

Transthyretin amyloid polyneuropathy, or ATTR-PN, is a rare progressive disease that damages the peripheral nerves and can cause symptoms like muscle weakness, numbness, and burning pain in the hands and feet.

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If you’ve been diagnosed with transthyretin amyloid polyneuropathy (ATTR-PN), you may have noticed symptoms like muscle weakness, numbness, and burning pain in your hands and feet.

ATTR-PN is a rare progressive disease that causes polyneuropathy (damage to peripheral nerves). These nerves carry messages between the brain and spinal cord and the muscles, skin, and organs.

Here’s what to know about muscle weakness in ATTR-PN, how to recognize changes early, and how to work with your care team to ease symptoms and slow disease progression while preserving your quality of life.

🗳️ Do you experience muscle weakness with transthyretin amyloid polyneuropathy (ATTR-PN)?

Yes

How Does ATTR Polyneuropathy Cause Muscle Weakness?

ATTR-PN is a type of amyloidosis, a rare disease in which the transthyretin (TTR) protein folds incorrectly. The misfolded proteins can stick together and form deposits called amyloid fibrils.

When amyloid fibrils build up in the peripheral nerves and the small blood vessels that supply them, they can damage the nerves and keep them from working properly. As this nerve damage progresses, it can lead to muscle weakness.

Early-onset ATTR-PN affects the small nerve fibers first. These nerve fibers help you sense pain and temperature changes. Damage to the small nerve fibers may cause pain, tingling, or burning.

This nerve damage usually affects the feet first. People with ATTR-PN may notice pain or trouble feeling temperature changes on the soles of their feet or in their toes. These symptoms may later move up the legs.

As ATTR-PN advances, symptoms may spread to the hands and arms. Large nerve fibers can also become damaged, affecting the ability to feel light touch and vibration, as well as where your body is positioned. Damage to motor nerve fibers can also cause muscle weakness and problems with movement.

Sensory and motor nerve damage can make walking and balance more difficult. Separately, damage to autonomic nerves — nerves that control automatic body functions — can affect blood pressure, digestion, and bladder function.

ATTR-PN can also begin later in life, and its symptoms can vary widely. Late-onset disease may affect both small and large nerve fibers and often causes sensory loss, pain, and muscle weakness. The age when symptoms begin and the way ATTR-PN progresses can vary depending on the specific TTR gene variant and other factors.

What Are the Symptoms of Muscle Weakness in ATTR-PN?

Symptoms are often symmetrical, affecting both sides of the body. When ATTR-PN affects nerves in the feet, you may experience pain, burning, or numbness. As nerve damage progresses, weakness and loss of sensation can make it harder to balance and walk.

ATTR-PN can also cause pain, numbness, tingling, or weakness in the hands and fingers. Some people also develop carpal tunnel syndrome, which happens when a nerve in the wrist becomes compressed.

Early-onset ATTR-PN begins by age 50 and may include:

Burning pain in the feet
Tingling or prickling feeling in the feet
A loss of temperature sensation in the feet
Shooting pain in the legs
Balance problems
Trouble walking
Dizziness

Late-onset ATTR-PN begins after 50 and may cause:

Numbness or tingling in the hands, sometimes related to carpal tunnel syndrome
Numbness or loss of sensation in the feet
Muscle weakness or wasting (loss of muscle size)
Balance problems
Difficulty walking

In addition, damage to autonomic nerves can cause problems with digestion, sweating, bladder function, and blood pressure. Hereditary ATTR amyloidosis can also affect organs beyond the nerves, including the heart and eyes.

Can ATTR Treatments Help Treat Muscle Weakness?

Although there’s currently no cure for ATTR-PN, treatments can slow disease progression and may slow the worsening of some symptoms, such as weakness.

The liver produces most of the TTR protein in the body. A liver transplant was once a main treatment for some people with hereditary ATTR amyloidosis because it greatly reduces the production of variant TTR. However, neuropathy and other problems can continue to progress after a transplant.

Today, medications are available to target the TTR protein. TTR silencers reduce the production of TTR, while TTR stabilizers help stop the protein from breaking apart and forming amyloid fibrils. Research has found that starting treatment as early as possible can slow the progression of polyneuropathy and may help preserve physical function.

If you have carpal tunnel syndrome, surgery may be recommended to relieve pressure on the median nerve in the wrist. This may help with muscle weakness in the hands and fingers related to carpal tunnel syndrome, but it doesn’t address the underlying ATTR-PN.

How Can You Manage Muscle Weakness From ATTR-PN?

One MyAmyloidosisTeam member said, “My neuropathy pain and weakness are making life difficult.” Your healthcare team can work with you to develop a treatment plan to manage symptoms and help you stay as active and independent as possible.

Your healthcare team will monitor you regularly for changes in muscle strength, balance, and walking. They may also recommend supportive care such as physical therapy and occupational therapy.

A physical therapist can develop an at-home exercise program to help you maintain strength, movement, and balance. An occupational therapist can suggest tools and strategies to make everyday activities such as eating, bathing, and dressing easier.

Being physically active may help preserve muscle strength and function. Because ATTR amyloidosis can affect the heart, talk with your healthcare team before beginning or changing a workout program.

In addition, consider joining a support group that can help you connect with others who understand life with ATTR-PN. “I’m glad to finally have people to talk to who understand and can relate to my symptoms,” one MyAmyloidosisTeam member shared. In-person or online groups can also provide support for family members and caregivers.