Hereditary transthyretin (hATTR) amyloidosis is a rare life-threatening disease caused by misfolded transthyretin (TTR) proteins. When the transthyretin protein becomes deformed and doesn’t take on its proper shape, it’s called misfolding. These abnormal proteins clump together to make fibrils that become stuck in organs throughout the body, causing several different symptoms. Depending on which parts of the body are affected, you may notice one or more sets of symptoms that can make diagnosing the disease difficult.

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These symptoms may show up in different ways at different times, or they may change or get worse as the disease progresses. It can take several years for enough amyloid fibrils to build up to cause noticeable symptoms, and the age when symptoms first appear can vary widely depending on individual factors. Because hATTR amyloidosis affects multiple systems in the body, the condition often affects not only physical health but also daily routines, independence, and quality of life. Activities such as walking, working, and even traveling may become more difficult over time.

In this article, we’ll discuss seven symptoms of hATTR amyloidosis to watch for. Because this condition can affect many parts of the body, it helps to know which symptoms may be related. Recognizing these signs can prompt you to see your doctor sooner so you can start treatment as quickly as possible.

1. Numbness or Tingling in Your Hands and Feet

Your nervous system is made of millions of delicate nerve cells that can be easily damaged by amyloid fibrils. Often, one of the first noticeable symptoms of hATTR amyloidosis is numbness or tingling in the hands and feet. These are signs of peripheral neuropathy. This condition results from damage to the peripheral nerves, a network of nerves that connect the brain and spinal cord (central nervous system) to the rest of the body. Symptoms like numbness and tingling usually start in the feet and slowly move up the legs. Over time, they may also affect the hands and spread up the arms. This pattern is often described as a “stocking-and-glove” distribution because it affects areas covered by socks and gloves.

Often, one of the first noticeable symptoms of hATTR amyloidosis is numbness or tingling in the hands and feet, which are signs of peripheral neuropathy.

Polyneuropathy is diagnosed when multiple peripheral nerves throughout the body are damaged by the buildup of transthyretin amyloid. As hATTR amyloidosis progresses, nerve damage may start to interfere with your ability to move and perform daily activities. You may lose voluntary control of your muscles, making it more difficult to walk or pick up objects. Some people also lose sensitivity to temperature or become extremely sensitive to pain.

2. Carpal Tunnel Syndrome

Studies have also found that carpal tunnel syndrome (CTS) in both wrists — known as bilateral CTS — can be an early sign of hATTR amyloidosis. Bilateral CTS can develop years before a person is diagnosed with hATTR amyloidosis. This can be an early warning sign of the condition. In amyloidosis, CTS occurs when amyloid fibrils build up in the tendons and nearby tissues, causing inflammation and pressing on the median nerve, a major nerve in your arm and hand.

Symptoms of CTS include:

• Pain or numbness in your hands
• Weak grip when picking up objects
• Numbness, burning, or tingling in your fingers, especially your thumb, index, middle, and ring fingers (often described as pins and needles)
• Swollen sensation in your fingers

CTS is a common condition affecting 1 percent to 5 percent of the population. Repetitive movements, hand or wrist injuries, and living with other bone or joint conditions can all contribute to CTS. For example, office work or rheumatoid arthritis may be the underlying cause of your CTS rather than amyloidosis.

If you notice new hand pain or weakness, particularly alongside other symptoms of hATTR amyloidosis, talk to your doctor. CTS can be painful and interfere with daily activities, so it’s best to seek treatment promptly.

3. Gastrointestinal Issues

Nerve damage from hATTR amyloidosis can also affect your autonomic nerves, which control automatic body functions like digestion and bladder or bowel activity. This type of nerve damage, known as autonomic neuropathy, can also be an early sign of hATTR amyloidosis, especially when it affects your stomach and intestines.

Gastrointestinal issues associated with hATTR amyloidosis include:

• Severe constipation
• Diarrhea
• Early satiety (feeling of fullness early in a meal)
• Nausea and vomiting
• Gastroparesis (slowed emptying of the stomach)
• Postprandial discomfort (feeling uncomfortable after eating, feeling full, or mild stomach pain)

For some people, these digestive problems may lead to unwanted weight loss over time.

4. Dizziness When Standing Up

Have you ever stood up too fast after sitting or lying down and become very dizzy or fainted? This may be due to orthostatic hypotension, which happens when blood pressure drops sharply when you stand up. Orthostatic hypotension affects 40 percent to 60 percent of people with hATTR amyloidosis. This happens because autonomic neuropathy can make it harder for your body to control blood pressure. When your blood pressure falls too low, you may feel lightheaded or dizzy — and in some cases, you might even faint.

The most common causes of orthostatic hypotension include lying in bed for a long time or being dehydrated. However, if these do not apply to you or if you’ve been feeling dizzy after standing, and this has been happening for weeks or months, it’s a good idea to call your doctor.

5. Shortness of Breath and Leg Swelling

Abnormal TTR proteins can build up in your blood vessels and heart, known as cardiac amyloidosis. The buildup of amyloid fibrils can lead to cardiomyopathy, a condition that makes it harder for your heart to pump blood properly. Over time, this condition can progress to congestive heart failure, where the heart muscle becomes stiff or enlarged, limiting blood flow to the rest of the body.

If you have cardiomyopathy or heart failure caused by hATTR amyloidosis, you may have symptoms such as:

• Shortness of breath due to fluid buildup in your lungs, even when sitting or lying down
• Fatigue (extreme tiredness that does not improve with rest)
• Lightheadedness or dizziness
• Edema (swelling in your feet, ankles, and legs)
• Pressure or discomfort in your chest

If you have hypertension (high blood pressure), high cholesterol levels, or a family history of heart disease, these factors may suggest a cause other than hATTR amyloidosis. Your doctor will evaluate these risks alongside your symptoms to determine the correct diagnosis.

6. Abnormal Heartbeat

Amyloid deposits in the heart can disrupt its electrical system, leading to an abnormal rhythm known as arrhythmia. This irregular heartbeat can occur in the atria (upper chambers) or ventricles (lower chambers) of the heart, potentially increasing your risk of heart failure and other complications. The specific symptoms of arrhythmia may vary depending on which part of the heart is affected.

Signs that you may have an arrhythmia include:

• Heart palpitations (fast, pounding, or fluttering heartbeat)
• Trouble breathing, especially when sleeping
• Weakness or fatigue
• Chest discomfort or pain
• Anxiety or feelings of unease
• Faintness or dizziness

7. Vision Problems

While most of your body’s TTR protein is produced in the liver, some is made by the cells in the retina, the back part of your eye. Around 10 percent of people with hATTR amyloidosis experience vision problems due to abnormal TTR proteins in the eyes. These symptoms often appear later in the disease as it progresses.

Vision and eye problems that develop in hATTR amyloidosis include:

• Floaters (dark spots or strings in your vision that move when you try to focus on them)
• Changes in your pupils (the dark center of your eyes)
• Enlarged or abnormal blood vessels on the conjunctiva (the clear outer layer of your eyes)
• Glaucoma (a condition that can increase pressure inside your eyes and damage the optic nerve)

Vision problems like glaucoma are more common in older adults and in people who have diabetes, high blood pressure, or a history of eye injuries. Your eye doctor can review your risk factors with you and perform an eye exam to figure out what’s causing your symptoms.

Early Detection and Treatment Are Key

The symptoms described in this article can be similar to those of other conditions, so getting an accurate diagnosis from a healthcare professional is important. Detecting hATTR amyloidosis early and starting treatment can help manage symptoms and improve quality of life. Acting early may also slow the progression of the disease and, in some cases, help you live longer. By addressing the buildup of amyloid fibrils before they cause serious organ damage, you may have a better chance of staying healthy for a longer time.

Detecting hATTR amyloidosis early and starting treatment can help manage symptoms and improve quality of life.

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