Signs and Symptoms of hATTR-PN

Living with unexplained health changes can feel like trying to solve a puzzle with missing pieces. Many people with hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) spend years visiting different doctors for what seem like separate issues.¹

You might see a foot doctor for numbness, a heart doctor for dizziness, and a stomach doctor for digestion problems. However, in hATTR-PN, these symptoms are actually connected.¹

The "dust on a wire" analogy

To understand why hATTR-PN causes so many different symptoms, it helps to look at how it works inside the body. Your liver produces a protein called transthyretin. In people with hATTR-PN, a genetic change causes this protein to "misfold" or take the wrong shape. These misfolded proteins clump together and form deposits called amyloid.¹

Think of your nerves as electrical wires that carry messages between your brain and your body. The amyloid deposits act like dust or grit building up on those wires. As the "dust" gets thicker, it causes short circuits. Because these nerves go everywhere – from your toes to your heart and stomach – the "short circuits" can happen in many different places at the same time.¹

The stocking-glove progression

The most common sign of hATTR-PN is polyneuropathy, which is damage to the nerves outside of your brain and spinal cord. This damage usually follows a specific pattern called "stocking-glove" progression:^1,2

• The feet and legs – Symptoms typically start in the toes and feet. You may feel numbness, a "pins and needles" tingling, or a sharp burning pain. As the condition moves forward, these feelings move up the legs toward the knees, much like pulling on a tall stocking.
• The hands – Once the symptoms reach the knees, they often begin in the fingertips. The numbness or tingling then moves up the arms toward the elbows, similar to putting on a glove.

It is important to tell these symptoms apart from "normal aging." General aches from aging usually stay in the joints. The burning and numbness of hATTR-PN are nerve-specific and tend to get worse over time.

More than just nerves

hATTR-PN is a multisystem condition. This means it affects more than just your sense of touch. There are "hidden" red flags that may seem unrelated but are often key pieces of the puzzle.^1,3

Bilateral carpal tunnel syndrome

Many people with hATTR-PN have surgery for carpal tunnel syndrome in both wrists. This often happens 5 to 10 years before any other symptoms appear. If you have had carpal tunnel in both hands, it may be a very early sign of amyloid buildup.^1,3

Dizziness and heart signs

The "dust" can also build up on the nerves that control your blood pressure and on the heart muscle itself. You might feel very dizzy or faint when you stand up quickly. This is called orthostatic hypotension. You may also feel short of breath or have an irregular heartbeat.^1,3

Digestive issues

The nerves that control your digestion can also be affected. This leads to unexplained stomach issues. Many patients experience alternating rounds of diarrhea and constipation, or feeling full after eating only a small amount of food.^1,3

Tracking your symptoms

The most important step you can take is to look at your symptoms as a group rather than separate problems. Doctors call this a "cluster of symptoms." If you have nerve pain in your feet AND heart issues OR stomach problems, it is time to speak up.

Use a notebook or a digital app to track these changes. Note when the numbness started and if you have other issues like dizziness or carpal tunnel. When you visit your healthcare team, show them the full list. Do not assume your heart doctor knows about your numb toes.

If you have a family history of these symptoms or if you recognize this cluster of "red flags," ask your doctor about genetic testing. A genetic test is a simple way to see if you have the change that causes hATTR-PN. Finding the cause early allows you to start a treatment plan that fits your specific needs.^3,4

Recognizing the patterns

hATTR-PN can be a confusing condition because it affects so many parts of the body at once. By understanding the "dust on a wire" mechanism, you can see why your heart, stomach, and nerves are all linked.¹

Recognizing the "stocking-glove" pattern and early signs like carpal tunnel can help you get answers sooner. Remember to track all your symptoms and share the complete picture with your healthcare provider.