Amyloidosis is caused by the misfolding of a protein called transthyretin (TTR). When this happens, the protein forms clumps called amyloid deposits. These deposits can build up in tissues and organs, causing damage and changing how they work. There are two main types of transthyretin amyloidosis (ATTR) — hereditary amyloidosis (hATTR) and wild-type amyloidosis (wild-type ATTR, or wtATTR).

Although these conditions can look similar, they differ in what causes them, who they affect, and how they’re treated. Read on to learn the differences between hATTR and wild-type ATTR.

1. A Genetic Mutation, Not Age, Causes hATTR

The biggest difference between hATTR and wild-type amyloidosis is what causes the TTR protein to misfold.

Hereditary amyloidosis is caused by a genetic mutation, or change, in the TTR gene. This mutation is passed down from parent to child in a pattern called autosomal dominant. This means a child only needs one copy of the mutation (from only one parent) to develop the condition. More than 120 TTR mutations have been identified, and some are more common in certain groups. Because of this genetic change, the resulting TTR protein becomes unstable and can misfold from the time it is made, no matter the person’s age.

Wild-type amyloidosis, on the other hand, is more common and is not inherited. It happens when normal TTR proteins become unstable with age. Over time, this leads to a buildup of amyloid deposits. Because it does not come from a genetic mutation, it isn’t passed from parent to child. It’s sometimes referred to as “age-related” or “senile” amyloidosis.

2. Younger People May Be Affected by hATTR

Hereditary and wild-type amyloidosis also differ in who is most likely to develop them and when symptoms typically appear.

Depending on the gene mutation, hATTR can appear earlier in life. Symptoms of hATTR amyloidosis can begin as early as age 20, though they can also appear much later, even into the 80s. Studies show that in the U.S., the median age of onset for hATTR amyloidosis is 68. This means half of people notice symptoms before 68, and half develop them after that age. People of any gender can be affected, since the mutation can inherited by any child.

Wild-type amyloidosis tends to develop later in life, usually after age 60. According to the Amyloidosis Research Consortium, it’s more common in men.

3. Wild-Type Amyloidosis Tends To Affect the Heart Only

Both types of ATTR amyloidosis cause a buildup of amyloid deposits in the body. They tend to affect different organs first.

The nerves, the heart, or both can be affected by hATTR amyloidosis. Some people have nerve-related symptoms (called polyneuropathy), such as numbness, tingling, or weakness in their hands and feet. The hereditary type often involves the autonomic nervous system, leading to symptoms like unexplained digestive issues (diarrhea, constipation), difficulty controlling blood pressure when standing, or sexual dysfunction. Others may develop heart-related symptoms, including shortness of breath, swollen legs, or irregular heartbeat. When ATTR amyloidosis affects the heart, it’s called transthyretin amyloid cardiomyopathy or ATTR-CM.

Wild-type amyloidosis usually affects the heart. This can make the heart walls stiff and thick. Some people also develop carpal tunnel syndrome, spinal stenosis, or a torn biceps tendon years before heart disease symptoms begin. These early signs appear before the heart is affected.

4. Genetic Testing Differentiates Between Each Type

Doctors diagnose ATTR amyloidosis using a combination of imaging, biopsies, and genetic testing.

If a TTR mutation is found, the diagnosis is hATTR amyloidosis. If no mutation is found and the amyloid deposits are made of normal TTR protein, the diagnosis is wild-type amyloidosis.

Because symptoms can look like other conditions, such as heart failure or neuropathy, ATTR is often misdiagnosed or delayed, especially in older adults. This is why it’s especially important to talk to a healthcare provider if you have a combination of these symptoms or have a family history of heart disease or unexplained nerve issues.

5. Some Treatment Options Are Only Approved for One Type

Treating both types of ATTR amyloidosis involves reducing amyloid buildup and managing symptoms. The U.S. Food and Drug Administration (FDA) has approved a few treatments for ATTR amyloidosis, but some are approved for just one type of ATTR amyloidosis. These treatments fall into two main groups — TTR stabilizers, which help keep the protein from breaking apart and misfolding, and gene silencers, which reduce how much TTR is made in the liver.

For people with hATTR, symptom care may also involve treating nerve pain and problems with the autonomic nervous system. This can mean taking medications to help control heart rate, blood pressure, or digestion.

Healthy habits can make a difference for both types, especially if your heart is affected. Your doctor may recommend reducing your salt intake and following other heart-healthy habits.

Your healthcare team can guide you on how lifestyle changes and treatment options can help you improve life with ATTR amyloidosis.

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