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For some people with transthyretin amyloidosis (ATTR amyloidosis), early symptoms — like tiredness, swelling, or numbness in the hands or feet — may seem mild, unrelated, just part of getting older. Because these symptoms can also come from other heart or nerve problems, ATTR amyloidosis often goes unrecognized for years. The good news is that with newer, noninvasive tests, doctors are now able to detect ATTR amyloidosis earlier and more accurately than ever before.
In this article, we’ll explain how ATTR amyloidosis is diagnosed. You’ll learn about the key tests used and how doctors tell ATTR amyloidosis apart from other types. We’ll also discuss why it’s important to find out whether you have the wild-type or hereditary form, as this helps guide treatment and next steps.
Amyloidosis is a group of diseases that develop when certain proteins in the body misfold (change shape) and stick together. These clumps are called amyloid deposits, and in amyloidosis, they build up in various tissues and organs.
There are several types of amyloidosis. Each is named for the protein that causes it. ATTR amyloidosis is caused by a protein called transthyretin (TTR), which is made in the liver. When TTR misfolds, it can form deposits in the heart and nervous system. There are two main forms of ATTR amyloidosis — wild-type and hereditary.
The most common form, wild-type ATTR (ATTRwt), isn’t inherited, which means it doesn’t run in families. It usually appears in older adults, especially men, according to the Amyloidosis Research Consortium. ATTRwt tends to develop slowly over many years.
Hereditary ATTR (hATTR) runs in families and is caused by a mutation (change) in the TTR gene. This follows an autosomal dominant pattern of inheritance, meaning each child of an affected parent has a 50 percent chance of inheriting the condition. Hereditary ATTR can start earlier in life than wild-type ATTR.
Both ATTRwt and hATTR can affect the heart, nerves, and other parts of the body. Symptoms depend on which organs are involved. For example, when amyloid builds up in the heart, it’s called transthyretin amyloid cardiomyopathy (ATTR-CM).
Because amyloidosis is rare and its symptoms can mimic other diseases, it’s often hard to recognize at first. Doctors look for certain red flags that suggest a possible diagnosis, including:
Risk is also higher in people with certain blood disorders, chronic (long-term) inflammation, or a family history of amyloidosis or nerve disease.
If signs or symptoms suggest ATTR amyloidosis, your doctor will perform a careful evaluation to find out whether amyloidosis may be the cause. The diagnostic process usually begins with a thorough medical history and physical exam. Your doctor may ask about your symptoms, family history, and any conditions that may raise your risk.
Blood and urine tests may also be ordered to check for signs of organ problems, especially in the heart or kidneys. Urine tests can help detect protein leaks or abnormal substances that may point to amyloid buildup.
The goal of this first step is to spot early warning signs and decide on the need for more specialized testing, including imaging tests, biopsy, and genetic testing.
Because amyloidosis often affects the heart, many people are referred to a cardiologist — a doctor who specializes in heart disease. The cardiologist will check how well the heart is working and look for signs that amyloid deposits may be causing stiffness or thickening of the heart muscle.
One of the first tests may be an echocardiogram. This painless test uses sound waves to create moving pictures of the heart. The results can reveal:
An electrocardiogram (ECG) may also be done to record the heart’s electrical activity. In amyloidosis, the ECG may show a low-voltage pattern. This means the heart’s electrical signals are weaker than expected. The results can help doctors tell ATTR amyloidosis apart from other causes of heart thickening, such as high blood pressure or inherited muscle diseases.
A cardiac MRI may be performed to create detailed images of the heart using magnets and radio waves. A special contrast dye highlights areas where amyloid has built up, showing how much of the heart is affected. This test is highly sensitive and specific for cardiac amyloidosis — it’s very good at both spotting amyloid and confirming it as the cause of heart stiffness.
Another specialized scan called a cardiac pyrophosphate (PYP) scan, or bone tracer cardiac scintigraphy, may also be used. This nuclear medicine scan uses a tracer typically used for bones. In ATTR amyloidosis, the tracer lights up ATTR amyloid deposits in the heart. If this scan is positive and blood tests rule out other causes, doctors may be able to diagnose ATTR without needing a biopsy.
A biopsy — taking a small tissue sample — is often needed to confirm amyloidosis. The tissue is examined under a microscope and stained with a dye called Congo red, which helps doctors see whether amyloid is present.
The least invasive option is an abdominal fat pad biopsy, in which a needle is used to remove a small sample of fat from the belly. This simple test can detect amyloid with little discomfort. Other biopsy sites may include the heart, salivary glands, or kidneys, depending on symptoms.
If amyloid is found, lab specialists perform additional tests — called immunohistochemistry or mass spectrometry — to identify the type of amyloid protein. These involve special stains that look for certain proteins or tools to analyze the protein’s structure. These methods help distinguish between ATTR amyloidosis (from the TTR protein) and light chain amyloidosis (known as AL amyloidosis).
If ATTR amyloidosis is confirmed, doctors may use genetic testing to learn which TTR gene change is responsible. There are more than 120 known TTR variants, and each can affect the body differently. Some mainly cause heart problems, whereas others involve the nerves.
Knowing the exact variant helps doctors:
People who carry a TTR mutation but don’t yet have symptoms may be monitored more closely or considered for early treatment or clinical trials. If no genetic variant is found, the diagnosis is wild-type ATTR.
Timing is everything. Getting an early diagnosis of ATTR amyloidosis can make a big difference. When the disease is caught early, treatment can start before serious damage occurs.
Starting treatment early gives the best chance to protect your heart, nerves, and other organs. For ATTR amyloidosis, new medications can stabilize or silence the TTR protein, helping slow or even stop the disease from progressing. However, these drugs generally can’t reverse damage that’s already been done.
The sooner amyloidosis is diagnosed, the better your long-term outcome can be. If you have lasting symptoms or a family history of amyloidosis, talk with your doctor. Early testing and care can help protect your organs and preserve your quality of life.
On MyAmyloidosisTeam, people share their experiences with amyloidosis, get advice, and find support from others who understand.
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