• Life expectancy with hereditary transthyretin (hATTR) amyloidosis depends on the specific gene mutation (changes) you have and your age at diagnosis.
• Historically, untreated hATTR amyloidosis had a median survival of 4.7 years, but newer treatments are significantly improving outcomes.
• New treatments are helping more people live longer with hATTR amyloidosis.

Hereditary transthyretin amyloidosis is a rare disease that creates abnormal transthyretin (TTR) proteins. These misfolded proteins clump together into amyloid fibrils, which build up in tissues and gradually damage the nervous system, heart, eyes, and gastrointestinal tract. However, advancements in treatment are improving survival significantly, with some people living more than a decade after diagnosis​​.

In studies from the previous 15 years, untreated hATTR amyloidosis showed a median survival rate of 4.7 years after diagnosis. This means that 4.7 years after diagnosis, half of the study participants were still alive. Individuals with certain genetic mutations and cardiomyopathy — a heart condition caused by amyloid deposits that stiffen the heart muscle and impair its function — had worse outcomes.

Fortunately, new treatments are extending the lifespan of those living with hATTR amyloidosis. These therapies help stabilize TTR proteins or stop your liver from making them, which prevents fibrils from collecting in your organs and causing dysfunction. Read on to learn how the life expectancy of those with hATTR amyloidosis has improved in recent years.

How Genetic Mutations Influence Life Expectancy

Hereditary transthyretin amyloidosis is an inherited condition passed down in families. Doctors and researchers have discovered more than 120 TTR gene mutations around the world that contribute to this disease. Two of the most common mutations are known as V30M and V122I. The type of gene mutation was once thought to determine which symptoms appear and how the disease progresses. However, scientists now understand that symptoms can vary and often affect multiple systems in the body.

V30M and Polyneuropathy

The V30M mutation is commonly associated with polyneuropathy, a condition where multiple peripheral nerves (those located outside the brain and spinal cord) are damaged. This can lead to symptoms like pain, weakness, or loss of sensation, often starting in the hands and feet. Polyneuropathy can significantly impact daily life, making activities like walking, gripping objects, or managing involuntary functions like digestion and blood pressure challenging.

Factors besides medications can also influence your prognosis while living with hATTR amyloidosis. Age and diet may affect your outlook and overall health.

Polyneuropathy can also affect autonomic (involuntary) functions, such as blood pressure regulation and digestion. This damage can lead to complications that can shorten a person’s lifespan if left untreated.

V122I and Cardiomyopathy

Nearly all people with the V122I mutation eventually develop ATTR-CM (transthyretin amyloid cardiomyopathy), a condition that reduces the heart’s ability to pump blood effectively. Amyloid fibrils build up in the heart, interfering with its ability to maintain rhythm and circulation. This buildup can lead to symptoms such as shortness of breath, fatigue, swelling in the legs, and difficulty exercising.

People with ATTR-CM caused by hATTR amyloidosis can eventually develop progressive heart failure or life-threatening arrhythmias (abnormal heart rhythms) if left untreated. Researchers have found that those with V122I mutations and heart involvement live, on average, 3.4 years after diagnosis.

New Treatments Extend Lifespan in hATTR Amyloidosis

The gold standard for treating hATTR amyloidosis since 1990 has been liver transplantation. The liver produces most of your body’s TTR protein. The transplanted liver doesn’t make abnormal proteins, so disease progression slows over time or even stops. In the past 25 years, liver transplants have significantly improved survival in those with hATTR amyloidosis.

As doctors and researchers continue to learn more about hATTR amyloidosis, they’re developing new treatments to help control symptoms, improve quality of life, and extend life span.

Although liver transplants are a very effective treatment, there aren’t enough donors available to meet the needs of people with other liver diseases. Fortunately, the U.S. Food and Drug Administration (FDA) has approved new hATTR amyloidosis therapies in recent years.

Some of the treatments are specifically approved for managing polyneuropathy caused by hATTR. They include:

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

Other medications are indicated specifically for treating cardiomyopathy of hATTR amyloidosis, including tafamidis (Vyndamax), ​​tafamidis meglumine (Vyndaqel), and acoramidis (Attruby). These treatments help stabilize the heart’s function by preventing further amyloid buildup.

These treatments were approved in just the past several years, so data on their long-term effects on survival is limited. As more people with hATTR amyloidosis begin treatment and stay on it longer, more studies can be performed to determine whether these drugs improve life expectancy.

Medications Have Improved Survival Rates

One large study of more than 3,000 people with hATTR familial amyloid polyneuropathy with V30M mutations examined survival rates with liver transplantation and tafamidis treatment. The study authors found that after 10 years studying people with early-onset hATTR familial amyloid polyneuropathy, nearly 96 percent of those treated with tafamidis were alive, and 73 percent of that group underwent liver transplantation. These findings highlight the potential of tafamidis to significantly improve survival, especially for those diagnosed early and at stage 1 of the disease. However, liver transplantation remains an important option for some early-onset cases.

According to a study in the journal Neurology, tafamidis treatment also improved survival across age groups. For individuals diagnosed before age 50 (early-onset disease), tafamidis reduced the risk of death by 91 percent compared to untreated individuals. In those diagnosed after age 50 (late-onset disease), tafamidis reduced the risk of death by 82 percent compared to those who did not receive treatment.

Other Factors That Influence Prognosis With hATTR Amyloidosis

Factors besides medications can also influence your prognosis while living with hATTR amyloidosis. Studies show that age and diet may affect your outlook and overall health.

The time of diagnosis can significantly affect the average life expectancy for those with hATTR amyloidosis and polyneuropathy. Older studies on the natural history of the disease show that individuals diagnosed with early-onset V30M mutations and polyneuropathy symptoms have an average survival of about 12 years. In contrast, those with late-onset disease typically live for around seven years after diagnosis if untreated. Early diagnosis and access to treatment can greatly improve these outcomes.

Although no research points to the benefits of specific diet changes in hATTR amyloidosis, the American Heart Association recommends a heart-healthy diet low in sodium for anyone living with cardiomyopathy or other heart conditions. Diets high in sodium or salt contribute to increased blood pressure, putting extra strain on your heart. Watching what you eat can help reduce your risk of other health complications, which may extend your lifespan.

New Treatments Provide Hope for Those With hATTR Amyloidosis

As doctors and researchers continue to learn more about hATTR amyloidosis, they’re developing new treatments to help control symptoms, improve quality of life, and extend lifespan. Clinical trials are studying new treatments, and researchers are learning more about therapies that are already approved. As more long-term studies continue, researchers will learn more about the treatments’ effects on survival.

You can take an active role to stay your healthiest and live longer with hATTR amyloidosis. Be sure to stay in touch with your healthcare team about any new symptoms you’re experiencing, along with any side effects from your medications. Your doctor is your partner in treating this long-term condition and improving your prognosis.

Talk With Others Who Understand

On MyAmyloidosisTeam, the social media network for people with amyloidosis and their loved ones, more than 2,500 members come together to ask questions, give advice, and share their experiences with others who understand life with amyloidosis.

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