What Is ATTR Amyloidosis?

Transthyretin amyloidosis, or ATTR amyloidosis, is a complex condition. It occurs when a normal protein in your body changes shape and builds up in your organs.¹

This protein, called transthyretin (TTR), becomes unstable, misfolds, and clumps together. These clumps are called amyloid fibrils. The fibrils then build up in parts of the body, most often the heart and nerves. This buildup can cause serious health problems over time.^1-3

ATTR amyloidosis is a rare condition. Understanding the basics is the first step in managing you or a loved one’s health. As you are learning more about this disease, you may see it go by different names. Some of them are: ^1-3

• Cardiac amyloidosis
• Amyloidosis ATTR
• Transthyretin amyloid cardiomyopathy (ATTR-CM)
• Transthyretin cardiac amyloidosis (ATTR-CM)
• TTR amyloidosis

Types of ATTR amyloidosis

ATTR amyloidosis has 2 main types:^1-4

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

Hereditary ATTR (hATTR)

This type is also called hATTR or variant ATTR. It is caused by a change, or mutation, in the TTR gene. This changed gene is passed down through your genes. If 1 parent has the gene mutation, there is a 50 percent chance their child will inherit it. ^1-3

Symptoms can start in adulthood, sometimes as early as age 30 or 50. This type can affect the nerves, causing polyneuropathy (hATTR-PN), or the heart, causing cardiomyopathy (hATTR-CM).^1-3

Wild-Type ATTR (ATTRwt)

This type is not passed down in families. It happens when the normal, or "wild-type," TTR protein becomes unstable as a person gets older. The exact cause is not fully known, but it is linked to the aging process.^1,3,4

ATTRwt mostly affects the heart (ATTRwt-CM). It is most common in men over the age of 60. Many people with this type also develop carpal tunnel syndrome, sometimes years before heart problems appear.^1,3,4

Prevalence of ATTR amyloidosis

​​ATTR amyloidosis is considered a rare disease. But many experts believe the condition is more common than we think. It is often underdiagnosed.^1-4

Misdiagnosis happens because the symptoms of ATTR amyloidosis can look like other, more common conditions. For example, shortness of breath or leg swelling may be blamed on simple "old age" or other types of heart failure. For people with ATTR amyloidosis, it can take an average of 3 years or more to get a correct diagnosis.^1-4

Because it is hard to diagnose, getting exact statistics on the condition is difficult. Here is what experts know:³

• Prevalence numbers vary widely around the world. But the disease is more common in Portugal, where it affects 1 in 538 people.
• Research shows that hATTR affects up to 6,400 people in the United States.
• The hereditary form (hATTR) is more common in certain races and ethnicities. For example, the V122I gene change is found in about 3 to 4 percent of African Americans.

Causes and risk factors

The main cause of ATTR amyloidosis is an unstable TTR protein. The TTR protein is mostly made in the liver. Its normal job is to carry thyroxine (a thyroid hormone) and vitamin A in the blood where it is transported throughout the body.^1-3

Normally, the TTR protein is a structure with 4 parts. In ATTR amyloidosis, this structure breaks apart. The individual parts misfold and stick together, forming the damaging amyloid fibrils.^1-3

The risk factors are different for each type.

Hereditary (ATTRv) risk factors: ^1-4

• Family history – The biggest risk factor is having a parent with the TTR gene mutation.
• Ancestry – Certain gene changes are more common in specific populations. This includes people of African, Portuguese, Irish, Swedish, and Japanese descent.

Wild-Type (ATTRwt) risk factors:^1,3,4

• Age – This type is strongly linked to aging. Most people are diagnosed after age 60 or 70.
• Sex – ATTRwt is much more common in men than in women.

Stages of ATTR amyloidosis

When ATTR amyloidosis affects the heart – known as ATTR cardiomyopathy (ATTR-CM) – doctors use staging systems. These systems help them understand how advanced the disease is. Staging also helps predict a person’s outlook and plan the best treatment.^5,6

A common system is the National Amyloidosis Centre (NAC) staging system. This system (and similar ones) uses the results of blood tests to check for biomarkers. Biomarkers are substances in the blood that show how the body is functioning.^5,6

The NAC system looks at 2 key biomarkers:^5,6

• NT-proBNP – This measures stress on the heart.
• eGFR (estimated glomerular filtration rate) – This measures how well the kidneys are working.

Based on the levels of these 2 markers, a doctor can place a person into a stage, such as Stage 1 (least advanced), Stage 2, or Stage 3 (most advanced). A 2024 study suggested adding a Stage 4 to this system to better find patients who are at a very high risk.⁶

Prognosis and outlook

The prognosis, or outlook, for a person with ATTR amyloidosis varies a lot. There is no single answer. Your personal outlook depends on many factors. These factors include:³

• The type of ATTR you have (hereditary or wild-type)
• Which organs are most affected (the heart, the nerves, or both)
• The stage of the disease when it is diagnosed
• Your specific gene mutation, if you have the hereditary type
• How early you start treatment

In the past, life expectancy was often stated as 3 to 15 years after symptoms begin. People with mainly nerve symptoms (polyneuropathy) often have a longer prognosis than people with heart symptoms (cardiomyopathy).³

It is important to know that these numbers are based on data from before today's newer treatments. The outlook for ATTR amyloidosis is changing. New therapies are now available that can slow the disease progression. Early diagnosis and starting treatment are the most important things you can do to improve your outlook.^1,4

A condition of growing awareness

While ATTR amyloidosis is considered a rare disease, awareness is growing, leading to better and earlier diagnoses. New treatments can help slow the buildup of amyloid and manage symptoms.

If you are experiencing symptoms or have a family history, talk to your doctor. An early and accurate diagnosis is the key to getting the right care.