Understanding Transthyretin Amyloidosis (ATTR): Types, Symptoms, and Diagnosis

Transthyretin amyloidosis (ATTR) is a rare, progressive condition that occurs when abnormal proteins build up in the body’s tissues. This buildup can damage critical organs, most notably the heart and nerves, leading to severe health complications. While the disease can be life-threatening, recent medical advancements and therapies have significantly improved patient outcomes by slowing or stopping the accumulation of these proteins.

What Exactly is ATTR?

To understand ATTR, it’s first essential to understand “amyloidosis.” Amyloidosis is a general term used when abnormal proteins build up in organs. ATTR is a specific type of this condition involving a protein called transthyretin (TTR).

Under normal conditions, your liver produces TTR, which travels through the blood to carry thyroid hormone and vitamin A (retinol) to various parts of the body. In ATTR, this protein becomes irregular or misshapen, forming clumps that deposit in tissues. These deposits damage the tissue and impair organ function.

The Two Main Types of ATTR

Medical professionals categorize ATTR based on how the condition develops: hereditary or wild-type.

Hereditary ATTR (hATTR)

Hereditary ATTR is an inherited condition passed down from one or both biological parents. It is caused by changes (variants) in the TTR gene, with over 120 known gene variants linked to the disease. Because it’s genetic, hATTR often affects multiple systems, including the nerves, heart, and kidneys. Symptoms can appear as early as age 30, though they typically manifest later in life.

Certain populations may have a higher prevalence of specific hATTR variants. For example, it is more common in parts of Sweden, Japan, Brazil, and Portugal. In the United States, the most common type occurs in 3% to 4% of all Black people, while other variants are more frequent in those of Irish ancestry.

Wild-Type ATTR (wATTR)

Unlike the hereditary form, wild-type ATTR does not run in families and involves no variant in the TTR gene. It typically develops as a person ages. WATTR primarily affects the heart but can also lead to peripheral neuropathy (pain and numbness in the hands and feet) and carpal tunnel syndrome. Some patients may experience forearm tendon rupture or lower spine issues before heart symptoms appear.

Impact on the Heart: ATTR-CM

When these protein deposits specifically target the heart muscle, the condition is known as Transthyretin Amyloid Cardiomyopathy (ATTR-CM). This is a potentially fatal disease where the heart walls become stiff.

This stiffness makes it tricky for the left ventricle to relax and fill with blood. As the disease progresses, the heart struggles to pump blood effectively, which ultimately leads to heart failure. Because the symptoms of ATTR-CM mimic general heart failure, it is frequently underdiagnosed.

Diagnosis and Testing

Because ATTR can affect multiple organs and mimics other conditions, a precise diagnosis is essential for determining the correct treatment path.

• Genetic Testing: For those suspected of having hATTR, genetic testing is used to identify the specific variant in the TTR gene. This information is vital for creating a tailored treatment plan.
• Clinical Evaluation: Doctors look for signs of nerve damage, kidney dysfunction, or heart stiffness.
• Imaging and Biopsy: These tools help confirm the presence of amyloid deposits in the tissues.

Summary and Outlook

Transthyretin amyloidosis is a complex, progressive disease that requires a multidisciplinary medical approach. While the buildup of irregular proteins can lead to severe cardiac and neurological impairment, the landscape of treatment is changing. Newer therapies are now available to help slow the progression of the disease, offering improved quality of life and better long-term outcomes for patients.