Hereditary forms of amyloidosis are caused by a mutated or abnormal type of protein, but wild-type ATTR is not caused by a genetic mutation. (1) (“Wild-type” in genetics refers to a sequence of DNA that is nonmutated, or a “normal” sequence of a healthy individual.) Unfortunately, there’s no way to explain what causes wild-type ATTR amyloidosis without diving into some tricky biochemistry. RELATED: Everything You Need to Know About the Different Types of Amyloidosis In people with hereditary forms of ATTR amyloidosis, the disease stems from a mutation of a genetic variant in the transthyretin gene that alters its function. But in wild-type ATTR, there is no genetic abnormality in the transthyretin gene that causes this error. Instead, a normal, wild-type form of transthyretin becomes prone to misfolding as a person ages, according to a 2017 paper. (3) Wild-type ATTR amyloidosis is much more common in males than females, with more than 90 percent of cases occurring in men, according to a 2022 paper. (4) Experts don’t know why the disease’s prevalence is so lopsided. There’s also some evidence that wild-type ATTR amyloidosis is a common driver of heart trouble, and therefore, Dr. Comenzo says, it’s likely that wild-type ATTR is not as rare as other types of the disease — though it’s still rarely diagnosed. While heart disease is one of the most widespread conditions among seniors, its cause is often never known. It’s possible that amyloidosis — especially wild-type ATTR — is causing or contributing to heart problems in a significant number of cases. (5) But it’s important to note that the prognosis for most people with wild-type ATTR is positive. This type of amyloidosis progresses slowly, and many individuals will never experience symptoms. (6) RELATED: What You Should Know About the Types and Symptoms of Heart Disease In men, it’s estimated that up to 1 percent of those over age 80 have misfolded amyloid proteins as a result of wild-type ATTR. But of this 1 percent, only about one in four will experience symptoms. Experts know all this from autopsy reports that have turned up wild-type amyloid deposits in the hearts and tissues of deceased men — many of whom never had any symptoms. (3) A similar type of amyloid deposits that develop on the brain, known as amyloid plaques, are being closely studied for their role in Alzheimer’s Disease, according to the National Institute on Aging. In 50 percent of people with the condition, these amyloid proteins accumulate in the tissues of the heart. (2) This can lead to problems with the way the heart muscle functions, and can cause symptoms including: (1)
Dizziness FatigueLeg swelling (edema)Shortness of breathUnusual heartbeatHypertensionProblems sleepingUnexplained weight lossNausea
If the protein buildup happens in the nerves, this can lead to pain, tingling, or loss of feeling around the body, often in a person’s arms or legs. In particular, carpal tunnel syndrome — numbness or tingling in the hand and arm — may show up among people with wild-type ATTR amyloidosis. In fact, carpal tunnel syndrome is often the earliest symptom of the disease. (1) In a small fraction of individuals, wild-type ATTR can cause protein accumulation in a person’s bladder, lungs, or bowels. But these patients typically don’t have any symptoms as a result of this buildup. (1) However, the terms “senility” and “senile” are no longer used generally because they carry a negative connotation and doctors now understand that heart disease, dementia, and other conditions that tend to affect seniors are often caused by underlying problems that may or may not be associated with the normal process of aging. RELATED: How Doctors Diagnose Amyloidosis Additionally, genetic testing is required to determine if TTR amyloidosis is caused by an accumulation of a mutated transthyretin protein or a wild-type (nonmutated) transthyretin protein. (1) Once someone is diagnosed, his or her doctor will likely treat the individual with diuretics to limit the kind of fluid buildup that causes limb swelling. A low-salt diet can also help because limiting salt reduces fluid retention. But treating the heart-related symptoms of wild-type ATTR is more difficult. Standard heart disease medications like beta blockers and calcium channel blockers don’t work well for individuals with wild-type ATTR and so are usually avoided. (3) In patients with potentially deadly heart problems related to wild-type ATTR, a heart transplant may be needed. (1) There is some research that supplements containing curcumin (a compound found in turmeric) or genistein (a component of soy) might be helpful. But further research is required to determine if these supplements are safe and truly effective. (7,8) There are a few available drugs to treat aspects of wild-type ATTR amyloidosis. In 2019, the U.S. Food and Drug Administration approved tafamidis (Vyndaqel) to treat cardiomyopathy (a type of heart disease affecting the heart muscle) associated with wild-type or hereditary ATTR amyloidosis. In most cases, doctors will use a variety of tests to monitor the progression of an individual’s wild-type ATTR amyloidosis, and they’ll treat any specific symptoms or side effects as they arise (1).
