Types of ATTR Amyloidosis

Learning you have ATTR amyloidosis can feel overwhelming. This condition has complex medical terms. Understanding your diagnosis is a powerful first step.

ATTR amyloidosis is a rare disease. It is caused by a protein made in your liver, called transthyretin, or TTR. When it is functioning normally, TTR carries vitamin A and a thyroid hormone called thyroxine through your blood.^1,2

In ATTR amyloidosis, however, this TTR protein becomes unstable. It breaks apart and folds the wrong way. These misfolded proteins clump together. The clumps are called amyloid fibrils. These fibrils build up in your body's organs and tissues. This buildup can cause serious damage to the heart and nerves over time.^1-3

There are 2 main types of ATTR amyloidosis: hereditary ATTR amyloidosis and wild-type amyloidosis. The type you have depends on why the TTR protein misfolds. Knowing your type helps you and your doctor make the best treatment plan for your health.^1-3

Hereditary ATTR amyloidosis (hATTR)

Hereditary ATTR amyloidosis is also called hATTR. This type is caused by a change in the TTR gene, also known as a genetic mutation. People with hATTR are born with this genetic mutation. They inherited it from 1 of their parents.^1-3

This faulty gene tells the body to make an unstable TTR protein. The protein misfolds easily. This can start happening in early or middle adulthood. More than 120 different mutations in the TTR gene can cause hATTR. The type of mutation can affect which parts of the body are most damaged.^1-3

The 2 main forms of hATTR are based on the main symptoms:

Hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN)

The "PN" stands for polyneuropathy. "Poly" means many. "Neuropathy" means nerve damage. In hATTR-PN, the amyloid fibrils build up mostly in the peripheral nerves. These are the nerves outside your brain and spinal cord. They control feeling and movement.^2,4

This nerve damage can cause many symptoms. Symptoms often start in the feet and legs. They can include:^1,2,4

• Numbness, tingling, or burning pain
• Weakness in the legs and arms
• Loss of feeling in the feet or hands
• Digestive problems, like diarrhea or severe constipation
• Dizziness when standing up

Symptoms of hATTR-PN often get worse over time. They can make walking and daily tasks very difficult.^1,2,4

Hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM)

The "CM" stands for cardiomyopathy. "Cardio" means heart. "Myopathy" means muscle disease. In hATTR-CM, the amyloid fibrils build up in the heart muscle.⁵

This buildup makes the heart walls thick and stiff. A stiff heart cannot pump blood to the body very well. This condition is a type of heart failure.⁵

Symptoms of hATTR-CM may include:⁵

• Shortness of breath, especially when lying down or with activity
• Swelling in the feet, ankles, and legs
• Extreme tiredness or fatigue
• An irregular or fast heartbeat, called arrhythmia
• Feeling dizzy or fainting

It is important to know that many people with hATTR have both nerve and heart symptoms. This is called a mixed type.²

Wild-type ATTR amyloidosis (ATTRwt)

Wild-type ATTR amyloidosis (ATTRwt) is the second main type. In ATTRwt, the normal TTR protein becomes unstable as a person gets older. It slowly misfolds and builds up in the body over many years. The exact cause is not fully known. It seems to be part of the aging process.^1,2,6

This type is not inherited. You cannot pass ATTRwt to your children.^1,6

Wild-type ATTR amyloidosis with cardiomyopathy (ATTRwt-CM)

ATTRwt almost always affects the heart. This is called ATTRwt-CM. The amyloid fibrils build up in the heart muscle. This causes the same stiffening and heart failure symptoms as hATTR-CM. Symptoms include shortness of breath, swelling, and fatigue.⁶

ATTRwt-CM is much more common than hATTR. It mostly affects older adults. It is most often diagnosed in men over the age of 60. Many people with ATTRwt-CM also have carpal tunnel syndrome. This is pain and numbness in the hand and wrist. It can be an early sign that appears years before heart symptoms.^1,6

Why knowing your type matters

There are 2 main types of ATTR amyloidosis. Hereditary (hATTR) comes from an inherited gene mutation. Wild-type (ATTRwt) is related to aging and does not involve a gene mutation.^1,3

These types can cause different problems. hATTR can affect the nerves (PN), the heart (CM), or both. ATTRwt mostly affects the heart (CM).^4-6

Your doctor will use tests to find out which type you have. These may include genetic tests, tissue biopsies, and special heart scans. Finding out your exact type is a key part of your diagnosis. It helps your healthcare team understand your condition. It also allows them to choose the treatments that will work best for you. Always talk to your doctor about your diagnosis and treatment plan.^1,3