Hereditary transthyretin amyloidosis (hATTR) is a rare disease that can cause serious symptoms in organs and systems in your body. It’s caused by a gene problem that’s passed down through families.
Most people who have hATTR will end up with damage to their nervous systems called polyneuropathy. That’s when you have problems with many of your peripheral nerves – the nerves in places in your body other than your brain and spinal cord.
hATTR symptoms get worse over time and can make it hard to get around and take care of yourself.
What Is Amyloidosis?
hATTR is a kind of amyloidosis. That’s a condition in which your body makes defective proteins that are the wrong shape.
Proteins play an important part in many functions of your cells. Misshapen proteins don’t work like they’re supposed to, and your body has a hard time getting rid of them. They gather together into clumps called amyloid deposits and build up in your organs and other tissues. Over time, that causes serious problems.
Different proteins are involved in different kinds of amyloidosis. With hATTR, the problem protein is called transthyretin (TTR).
The TTR Protein
Transthyretin is made mainly in your liver, but also your brain and eyes. Its job is to carry vitamin A (retinol) and the thyroid hormone thyroxine through your bloodstream to the places they’re needed.
In hATTR, the gene that controls the production of transthyretin has a mutation, or change, that causes the protein to be unstable. It breaks down and “folds” into the wrong shape.
Dozens of mutations can lead to hATTR. Which mutation you have determines what parts of your body are affected. Among the most common:
V30M. This mutation causes symptoms mainly in your nervous system. It’s most common among people with ancestry from Portugal, Spain, France, Sweden, or Japan.
V122l. As many as 4% of people of West African descent are estimated to carry this gene mutation. It causes mainly heart problems.
T60A. This mutation causes heart and nerve problems. It’s most common among people with Irish ethnicity.
While polyneuropathy and heart problems are the most common symptoms of hATTR, it can also affect your digestive system, kidneys, and eyes.
Amyloid Deposits and Organ Damage
Normally, once proteins do their job, they’re broken down and removed from your bloodstream. When you have amyloidosis, your body can’t use the defective proteins, or dispose of them.
They get tangled together into long, stiff strands called fibrils. Those stick together and form amyloid, which builds up in your organs and other tissues.
Amyloid deposits cause damage that makes it hard for your organs to work the way they’re supposed to. The substance can make your heart muscle hard and less flexible, so it doesn’t pump well. It can clog the filtering mechanism in your kidneys, allowing toxins to build up in your blood.
With your nerves, amyloid can break down the nerve fibers and cause them to misfire. It can also cause swelling in surrounding tissues that press on nerves. That leads to a range of symptoms, from tingling and burning pain in your feet and hands to muscle weakness and loss of coordination.
How hATTR Is Passed Down
Your DNA is made up of many thousands of genes that come in pairs. You get one of each pair from your father and the other from your mother. If either one of them has a mutation in the gene that controls the production of TTR, you have a 50% chance of having the same mutation.
But, just because you carry the problem gene doesn’t mean you’ll ever develop the disease. It depends a lot on which gene mutation you have. Your family history and ethnicity also play a role.
hATTR is much more common in some parts of the world than in others. Some variations cause symptoms in almost everyone who has the gene mutation. With others, it’s less than half.
Many people who learn that a parent or other close relative has hATTR choose to have their genes examined through a blood test to see if they carry one of the mutations that cause the disease. A genetic counselor can help you understand the results and your individual risk of getting symptoms.
Not everyone wants to know if they’re at risk. But finding out can put your mind at ease and help you make plans for your future medical needs.
Show Sources
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SOURCES:
Amyloid Research Consortium: “Disease Overview: Hereditary Transthyretin Amyloidosis,” “Neuropathy in Amyloidosis Symptoms and Management.”
Neurology and Therapy: “A Narrative Review of the Role of Transthyretin in Health and Disease.”
Mayo Clinic: “Peripheral neuropathy.”
StatPearls: “Transthyretin Amyloid Cardiomyopathy (ATTR-CM).”
Cleveland Clinic: “Amyloidosis.”
Amyloidosis Foundation: “Hereditary Amyloidosis.”
