The human body is made up of an estimated 30 trillion cells. Within each cell are strands of DNA called genes. Each gene contains specific instructions that tell your cells to make proteins that, in turn, perform all sorts of specific tasks within your body, from fighting off infections to your eye color. That’s why when a gene variation (often called a mutation) happens, it can cause the body to miscommunicate or malfunction. This is what often happens if you’re born with a rare disease, such as hereditary transthyretin amyloidosis (hATTR) with polyneuropathy.
Amyloidosis is the term for a group of rare diseases that cause abnormal fibrous deposits (called amyloid fibrils) to build up in tissues and organs. Amyloid is produced when abnormal proteins in the body “misfold” and collect together. As the amyloid builds up, it starts to cause damage to the heart, liver, or other organs. When the malfunction has no exact cause, it’s called wild-type ATTR. When it’s caused by a genetic malfunction, it’s called hereditary ATTR or hATTR. To determine whether your ATTR is wild-type or genetic, genetic testing is required.
Genetic Testing for hATTR
Today, genetic testing for hATTR is easily available through a variety of labs. Usually, your doctor orders the test and pinpoints which genes should be looked at.
Test results can confirm or rule out hATTR and help you understand the probability of getting or passing on the disease. But they can’t predict at what point in your life symptoms will happen, how serious they might be, or how long it’ll take for them to get worse.
Because it can be passed along through families, genetic testing is suggested for people who might have hATTR even when you don’t have symptoms. The American Heart Association reports that about 50,000 people worldwide have hATTR. But the number may be higher since hATTR shares symptoms with other more common conditions, such as nerve damage and heart failure, and can be misdiagnosed. Medical experts recommend genetic testing if you:
- Have biopsy-confirmed ATTR amyloidosis
- Are a carrier of the TTR gene variant but don’t have symptoms
- Have unexplained, worsening symptoms that are typical in hATTR amyloidosis, such as peripheral neuropathy (damage to nerves in the hands, feet, or lower legs), congestive heart failure or other chronic heart conditions, or recurrent urinary tract infections, excessive sweating, unintended weight loss, and other issues with the autonomic nervous system that regulates bodily functions
- Have a parent, sibling, or child who has been diagnosed with hATTR
Genetic testing for hATTR requires a sample of blood or saliva and should only be done in adults. It is usually suggested that you meet with a genetic counselor to review your family history and help you understand the results and what they mean.
Insight for Family Members
Certain areas of the world have a greater concentration of the disease. The Amyloidosis Research Consortium says hATTR happens more often in certain parts of Portugal, Brazil, Sweden, and Japan. In the United States, as many as 6,400 people have hATTR. In Americans of European descent, it happens in one in 100,000 people. The disease is more common in northern Portugal, where it affects one in 538. It’s also found more often in people of African and Irish ancestry. But it’s not limited to these groups. It has been found across all ethnicities and happens equally in men and women.
Noel Dasgupta, MD, knows the ins and outs of genetic testing for hATTR. As an associate professor of pathology and laboratory medicine at Indiana University, she recently co-wrote an in-depth scientific article about the diagnostic process and its benefits.
“In the United States, 3%-4% of African Americans may have a genetic change that puts them at risk for developing signs and symptoms of transthyretin amyloidosis,” Dasgupta says. “Early diagnosis and treatment could help prevent serious disability from the disease.”
Genetic testing can also provide important information to your immediate family about the risks they may have for getting hATTR. For this reason, Dasgupta advises genetic testing for first-degree relatives (parents, siblings, and children) of people diagnosed with hATTR.
“If one parent has hATTR, 50% of their children are at risk for inheriting the gene,” Dasgupta says. “However, if you have wild-type transthyretin amyloidosis, because the transthyretin gene is normal, other family members are not thought to be at increased risk for developing amyloidosis.”
It is also possible to have the gene variation for hATTR and never get symptoms but still pass it along to your children. This makes genetic testing even more important if you have family members who have been diagnosed with the disease.
“Symptoms of the disease usually do not occur until after age 40,” Dasgupta says. “If you are asymptomatic, it is useful to follow up regularly with a doctor who can determine if a patient is developing early symptoms which could be very mild, and the patient may not recognize.”
Although genetic testing for hATTR can provide important information about your health and that of your loved ones, learning you have a rare disease can also bring up stress and difficult emotions. For this reason, Dasgupta recommends working with a genetic counselor to help you understand the results and next steps.
There are other implications as well. “Genetic testing results do not currently affect your ability to obtain health insurance,” Dasgupta says. “But it could affect your ability to obtain life insurance or disability coverage.”
It’s important to weigh the potential financial impact with the benefit of having important knowledge about your body that could help you find meaningful treatment.
Hope for More Effective hATTR Treatment
Right now, there are more than 120 mutations in the TTR gene that have been identified. Each mutation causes a different pattern of how the disease begins, its symptoms, and its progression. Genetic testing for hATTR can provide you and your doctors with a clearer understanding of how the malfunctioning proteins may affect your body so you can receive the best possible treatment.
“In recent years, effective therapies for ATTR cardiomyopathy and neuropathy have been developed,” says Kevin Alexander, MD, assistant professor of cardiovascular medicine at Stanford University School of Medicine. “These treatments are most effective when started in the early stages of disease. So early diagnosis is crucial to have the best outcomes for patients.”
Dasgupta says that some treatments are only approved for hereditary forms of transthyretin amyloidosis, so a positive genetic test may affect your ability to get specific therapies.
“In patients with signs and symptoms of transthyretin amyloidosis, earlier diagnosis and treatment can potentially prevent severe organ failure,” she says. “Treatments are most effective in preventing severe disease symptoms and disability if started earlier in the disease process. Treatment is currently only available for symptomatic individuals. The therapies, however, are rapidly being developed and in the future, it may be possible to prevent the patient from developing signs and symptoms or reverse any damage.”
Since the first case of hATTR was described in the 1950s, a lot more is known about this rare disease. With all we understand now about our bodies on a cellular level, rare diseases that were once a mystery are now – if not curable – understandable and often treatable once we have the genetic test in hand.
Show Sources
Photo Credit: Westend61/Getty Images
SOURCES:
PLoS Biology: “Estimates for the Number of Human and Bacteria Cells in the Body.”
Genes & Health: “Genes Made Easy.”
Prion: “Amyloid fibrils: abnormal protein assembly.”
Noel Dasgupta, MD, FACC, associate professor of clinical medicine and pathology & laboratory medicine, Indiana University.
HATTR Awareness: “Symptoms and Diagnosis.”
Amyloidosis Research Consortium: “About Amyloidosis,” “Hereditary Transthyretin Amyloidosis: Disease Overview.”
American Heart Association: “Genetic Testing and Counseling for hATTR Amyloidosis,” “What is hATTR Amyloidosis?”
Therapeutics and Clinical Risk Management: “Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines.”
Advances in Therapy: “Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK.”
Current Opinion in Cardiology: “Clinical approach to genetic testing in amyloid cardiomyopathy: from mechanism to effective therapies.”
Kevin Alexander, MD, FACC, FHFSA, assistant professor of cardiovascular medicine, Stanford University Medical Center.
Orphanet Journal of Rare Diseases: “Abstracts from the First European Meeting for ATTR Amyloidosis for Doctors and Patients: Paris, France.”
