Signs and Symptoms of ATTR Amyloidosis

ATTR amyloidosis happens when a protein in your body, called transthyretin (TTR), breaks apart and builds up in your organs. This buildup can cause many different symptoms.¹

Understanding these signs is a key step in managing the condition. Different types of ATTR amyloidosis create different symptoms.¹

What is ATTR amyloidosis?

Your body makes a protein called transthyretin, or TTR. This protein carries thyroid hormone and vitamin A in your blood. In ATTR amyloidosis, the TTR protein becomes unstable. It breaks apart and folds the wrong way. These misfolded proteins clump together.^1,2

The clumps are called amyloid fibrils. These fibrils build up in different parts of the body. They can damage the nerves, heart, and other organs. This damage causes the symptoms of the disease.^1,2

There are 2 main types of ATTR amyloidosis. They are:^1,2

• Hereditary ATTR (hATTR)
• Wild-type ATTR (ATTRwt)

Hereditary ATTR (hATTR)

This type is passed down in families. A person is born with a mutation in the gene that makes the TTR protein. This change makes the protein very unstable. Symptoms can start at different ages, sometimes as early as your 30s or 40s.^1,2

Wild-Type ATTR (ATTRwt)

This type is not passed down in families. People with ATTRwt are born with a normal TTR gene. For reasons that are not clear, the normal TTR protein becomes unstable as a person gets older. This type usually affects men over the age of 60.^1,2,4

Symptoms of hereditary ATTR (hATTR)

Hereditary ATTR amyloidosis can affect many parts of the body. The symptoms often depend on which organs are most affected. Doctors sometimes group hATTR by the main symptoms. The 2 most common groups are polyneuropathy (nerve damage) and cardiomyopathy (heart damage). Many people have symptoms of both.^1,2

hATTR with polyneuropathy (hATTR-PN)

Polyneuropathy means "disease of many nerves." This type happens when amyloid builds up in the nerves outside of the brain and spinal cord. These are called the peripheral nerves.^1,2

Symptoms of hATTR-PN often include:^1,2

• Numbness, tingling, or burning pain in the feet and hands
• Weakness in the legs and arms
• Loss of feeling for hot and cold

Amyloid can also damage the autonomic nerves. These nerves control body functions you do not think about. Symptoms of autonomic nerve damage include:^1,2

• Stomach and gut problems, such as diarrhea, constipation, or feeling full very quickly
• Dizziness or fainting when standing up
• Problems with bladder control

Carpal tunnel syndrome is also very common. It causes pain, numbness, and tingling in the hand and wrist. It can be an early sign that appears years before other nerve issues.^1,2

hATTR with cardiomyopathy (hATTR-CM)

Cardiomyopathy means "disease of the heart muscle." This happens when amyloid fibrils build up in the heart. The heart muscle becomes thick and stiff. This makes it hard for the heart to pump blood.^1-3

Symptoms of hATTR-CM often include:^1-3

• Shortness of breath, especially when you are active or lying down
• Feeling very tired or weak (fatigue)
• Swelling in the legs, ankles, and feet (edema)
• An irregular or fast heartbeat (arrhythmia)
• Chest pain

Symptoms of wild-type ATTR (ATTRwt)

Wild-type ATTR amyloidosis almost always affects the heart. It is a major cause of cardiomyopathy in older adults. Because it is linked to aging, it used to be called senile systemic amyloidosis. We now call it wild-type ATTR cardiomyopathy (ATTRwt-CM).^1,4

The symptoms of ATTRwt-CM are the same as hATTR-CM. They are caused by the stiffening of the heart muscle. Symptoms of ATTRwt-CM include:^1,4

• Shortness of breath
• Extreme fatigue
• Swelling in the lower legs and feet
• Irregular heartbeats

People with ATTRwt-CM often have other signs that can appear earlier. These are sometimes called "red flags." These signs can include:^1-4

• Carpal tunnel syndrome – This is very common. Many people have surgery for it 5 to 10 years before they have heart symptoms. Having carpal tunnel syndrome in both hands should make one think about possible amyloid in the right settings.
• Spinal stenosis – This is a narrowing of the spaces in the spine. It can cause back and leg pain.
• Tendon ruptures – This is when tendons in the body, like the upper arm, tear, sometimes with little or no injury.

Talk to your doctor

ATTR amyloidosis causes a wide range of symptoms. The signs depend on the type of ATTR and which organs are affected. Hereditary ATTR can damage the nerves (hATTR-PN) or the heart (hATTR-CM). Wild-type ATTR (ATTRwt) mostly damages the heart.

Recognizing these symptoms, like nerve pain, shortness of breath, or carpal tunnel syndrome, is very important. Always talk to your doctor about any new or worrying symptoms. They can help you get the right diagnosis and get the right care.