A genetic variant is a change that occurs in the DNA sequence. Genetic variants can lie inside one of these coding genes and can form sporadically, meaning they just pop up by chance. They can form in response to some form of environmental exposure, such as air pollution or tobacco smoke. They can also be inherited from one or both parents. (2) While most variants are harmless, some can cause or contribute to the formation of disease. (2) Most types of amyloidosis (a disorder characterized by the abnormal buildup of amyloid protein) are not caused by an inherited genetic variant and may occur in association with other disorders. There are two types of hereditary amyloidosis that are caused by an inherited genetic variant. These two subtypes of hereditary amyloidosis are known as familial transthyretin-associated amyloidosis (ATTR amyloidosis) and non-TTR amyloidosis (2). As with all forms of amyloidosis, ATTR amyloidosis is a result of the erroneous folding of protein molecules. These misfolded proteins aggregate and are called amyloids, and amyloids can accumulate in different parts of the body and cause problems. (3) ATTR amyloidosis tends to show up in adults ages 20 to 70, and its symptoms can range from mild to severe. (4) If ATTR amyloidosis symptoms are very mild, someone could live a normal, healthy life with the disorder never knowing they have it (and without it ever causing problems). (3) Other cases cause much more serious problems. While ATTR amyloidosis tends to be considered a rare disease — and one that develops in just 1 out of 100,000 people in the United States — there’s one variation of ATTR that seems to be common in people of African-American descent. There’s some evidence that 4 percent of African-Americans carry this gene variant, which puts them at greater risk for heart trouble. (3) It’s also important to note that there are many different varieties of ATTR amyloidosis that can affect multiple organ systems of the body — all involve the misfolded proteins that build up to form amyloid protein. ATTR amyloidosis can be grouped into three main categories, based on their symptoms and the parts of the body they strike: (4) That said, most cases of non-TTR amyloidosis tend to involve genes that play a role in kidney function, which sometimes leads to kidney damage and disease. Other symptoms include liver or heart trouble, nerve and muscle pain, and GI issues like constipation and diarrhea. (3) RELATED: Everything You Need to Know About Amyloidosis Diagnosis Treatment for these types of amyloidoses depends on a patient’s condition. Along with drugs to manage heart damage, nerve pain, or other symptoms, there are also some treatments that can stop the production of amyloid in some patients, potentially slowing or stopping the progression of the disease. (6) Such treatments may include liver transplant, as well as the drug patisiran (Onpattro) — the first approved by the U.S. Food and Drug Administration (FDA) to treat hereditary amyloidosis. Some other drugs are also currently being investigated in clinical trials. Also, if a person has inherited one of the gene variants that cause hereditary amyloidosis, there’s a good chance they will have a family history of heart disease, liver or kidney problems, or some of the other health concerns mentioned above. (7) But that’s not always the case. The genetic variants that cause ATTR and non-TTR amyloidosis can also be “de novo,” meaning they occur by chance instead of being inherited from a parent. But even though these genetic variants are not inherited, they can still be subsequently passed down to a patient’s biological children. Can hereditary amyloidosis be deadly? Yes, it can be. All types of amyloidosis can lead to organ disease and failure, which can be fatal. But again, all types of the disease are rare. That said, if the symptoms and complications mentioned here sound familiar — and especially if they seem to run in your family — tell your doctor. (3)
