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By Jennifer Schumacher, PhD and Leslie Amass, PhD - This article originally published on Get Healthy Stay Healthy

You probably know someone with a heart condition, GI problems, or nerve pain. But chances are you don’t likely know someone with a rare and life-threatening disease that can cause many of these conditions to occur together—this disease is called transthyretin (TTR) amyloidosis.

TTR amyloidosis is so rare that it is estimated to affect one in 100,000 Americans of European descent. Many experts, however, think that the disease is not rare, and that it is just under diagnosed due to a lack of awareness. Because TTR amyloidosis is not well known or understood, and because its symptoms are so similar to other more well-known conditions, the disease is not so easy to recognize.

What’s TTR Amyloidosis?
Amyloidosis, in general, is a disease caused by a buildup of abnormal, “misfolded” proteins in the body called amyloid. Amyloid can be deposited throughout the body’s tissues, which can cause organ damage. Amyloidosis symptoms are often vague or seem similar to symptoms caused by other conditions, and can vary depending on the type and location of the amyloid deposits.

TTR amyloidosis is a specific type of amyloidosis that is very rare. TTR stands for transthyretin, a protein that is primarily made in the liver. TTR amyloidosis occurs when this protein “misfolds” or changes its shape in an abnormal way, and forms into fibrous clumps. Depending on the specific type of TTR amyloidosis, the amyloid is deposited into various organs and/or nerves, which can lead to permanent damage and organ malfunction.

TTR amyloidosis has two forms: hereditary and non-hereditary. The hereditary form is caused by a genetic mutation inherited from a family member. The non-hereditary form, also called “wild-type,” emerges from a normal transthyretin molecule that (for reasons unknown) becomes unstable and misfolds, forming amyloid.

The Nerves and Heart
TTR amyloidosis can involve the nerves and/or the heart, though other organs and systems may be affected at the same time.

The most common forms of TTR amyloidosis are:

  • TTR Familial Amyloid Polyneuropathy (TTR-FAP) primarily affects the nerves and is caused by mutations in the TTR gene passed on from the affected mother or father. This means the child of a person with the TTR mutation has a 50% chance of inheriting it. The TTR mutation is present from birth; however, symptoms of the disease show up in adulthood, typically in people between ages 20 and 70. Not everyone with the abnormal gene will develop TTR amyloidosis; the reason for this is not known.

Amyloid build up occurs primarily in the nerves that detect touch, pain, heat, and sound. It can cause loss of sensation, tingling, numbness or pain in the hands and feet (also known as peripheral neuropathy). People with TTR-FAP often also experience symptoms that affect multiple bodily systems at the same time, such as diarrhea, constipation, nausea, vomiting, unintended weight loss, feeling full quickly after eating, sexual dysfunction, urinary incontinence, headaches, dizziness, sudden drop in blood pressure upon standing, and carpal tunnel syndrome. Some people also experience problems with their heart, eyes, and kidneys. TTR-FAP affects men and women equally.

  • TTR Cardiomyopathy (TTR-CM) primarily affects the heart, as amyloid builds up in the muscles surrounding the heart and affects the heart’s ability to function properly. Its symptoms often resemble those of other heart conditions (e.g., heart failure, enlarged heart, irregular heart beat) and may include: fatigue, swelling, shortness of breath, low blood pressure, and a general feeling of illness. Some people, however, do not experience symptoms until later into their disease. Buildup of amyloid in the heart muscle can cause weakness and lead to heart failure and death. In some cases, people may also experience nerve pain. Symptoms usually begin at 50 or 60 years of age.

It exists in hereditary and non-hereditary forms. More than 27 gene mutations leading to TTR-CM have been identified. The most prevalent mutation is V122I, which affects primarily African-Americans or people of African descent worldwide.

How Do You Treat It?
There is no cure for TTR amyloidosis. Treatment for the disease is a two-fold process: treat the underlying cause and manage symptoms. For TTR-FAP, liver transplant and medicines that work by stabilizing and preventing the TTR protein from misfolding are available in some countries. For both TTR-FAP and TTR-CM, investigational treatments may also be available through clinical trials.

Research is underway to better understand this disease and to discover treatments. For more information about available clinical trials for amyloidosis, go to or Pfizer: Find a Trial.

What You Can Do
Speak to your doctor if you believe you or a family member may have TTR amyloidosis. It’s a progressive disease, meaning that you cannot reverse the condition and it worsens over time. The more advanced the disease, the more debilitating it is. So it’s important to get an accurate diagnosis and treat the condition early on.

A number of tests (e.g., biopsy, genetic) may need to be run in order to determine a correct diagnosis. It’s also important to work with a healthcare team who specializes in diagnosing TTR amyloidosis.

If TTR amyloidosis is suspected, be prepared to talk to the doctor to understand the disease and how it may affect you. And keep in mind that not everyone with a gene mutation will develop the disease. An open conversation with the genetic counselor can help you decide whether to get genetic testing and to determine a plan of action for you and your family to consider.

Leslie Amass, Ph.D. and Jennifer Schumacher, PhD are Medical Directors within the Rare Neuroscience Team, Global Innovative Pharma Business, at Pfizer, Inc.

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