Hereditary ATTR (hATTR) amyloidosis is passed down through families.
Hereditary ATTR amyloidosis is caused by a change or mutation in the transthyretin (TTR) gene which is inherited (i.e. runs in families). This change makes the TTR protein unstable so it folds the wrong way and attaches and builds up in different organs and tissues as amyloid.
TTR protein is mostly made in the liver. Its role is to transport a hormone and vitamin A (thyroxine and retinol) around the body, which is why it’s called transthyretin.
Watch this 3D animated overview of ATTR amyloidosis:
You can download and print our Hereditary ATTR Overview packet by clicking here.
Everyone makes the TTR protein, but when the gene is mutated, the protein is more likely to form amyloid build up. There are many different gene mutations linked to hereditary ATTR amyloidosis. One of the most common is called V122I, which is especially common in people of African descent.
There are over 120 different mutations in the TTR gene but, as research continues, it is possible that more may be identified. Each different mutation causes a different pattern of disease onset, symptoms and outlook. The most common ATTR mutations are the:
- ATTR V30M variant – found mostly in Portugal, Spain, France, Sweden, Japan and descendants of these regions
- ATTR V122I variant – seen in 3-4% of African Americans
- ATTR T60A variant – seen in people of Irish descent and the most common variant in the UK
In this video, Dr. James Ampadu, cardiologist at Prisma Health in South Carolina, gives an introduction to hereditary amyloidosis and what it means for you and your family.
You can download the slides from Dr. Ampadu’s video above by clicking here.
Diagnosis, Symptoms, and Treatment
When doctors suspect ATTR amyloidosis, they use several tests to confirm it. One common test is a small tissue sample from the abdominal fat pad to check for amyloid deposits. Other tests look at how amyloid is affecting the heart, nerves, and other organs. These can include blood work, nerve and muscle tests, echocardiogram, MRI, and other scans. Sometimes doctors may need to biopsy an organ.
Hereditary ATTR amyloidosis is confirmed with a blood test that shows a mutation in the TTR gene. This test also identifies which variant is present. Since hereditary ATTR amyloidosis is passed down in families, genetic testing can help find relatives who may carry the changed gene.
If someone is found to have the mutated gene, doctors will do more tests to check for signs of the disease. These tests are repeated over time to monitor for the disease. Genetic counseling and testing can give families and individuals important guidance.
Symptoms of hereditary ATTR amyloidosis depend on the gene variant, which organs are affected, and how much damage has built up. Symptoms can appear at any age in adulthood. Common symptoms include:
- Cardiomyopathy – Heart problems such as shortness of breath, irregular heartbeat, ankle swelling (edema), fainting, fainting, or chest pain (angina)
- Peripheral neuropathy – Nerve problems in the legs and feet such as tingling, numbness, weakness, pain, or trouble walking
- Autonomic neuropathy – Autonomic nerve problems such as feeling light-headed when standing (orthostatic hypotension), bladder issues, bowel issues, or sexual dysfunction
- Gastrointestinal – Digestive problems such as decreased appetite, diarrhea, nausea, stomach pain, or weight loss
Some gene mutations are associated with specific symptoms. For example, the “V30M” variant typically causes symptoms associated with peripheral neuropathy, whereas the “V122I” variant typically causes symptoms associated with cardiomyopathy. Still, most people will have symptoms affecting more than one organ, no matter which variant they have.
For many years, a liver transplant has been the only option for treatment of hereditary ATTR amyloidosis. TTR is mostly made by the liver, and a transplant will reduce the production of the abnormal TTR protein.
More recently, several drugs exist for the treatment of hATTR, some of which are still investigational and some of which are FDA approved. These treatments each have different therapeutic approaches and are aimed at:
- Stabilizing the TTR protein
- Stopping the production of TTR protein
- Removing the amyloid deposits
Stabilizing the TTR protein
The approach of TTR stabilizers is to stop the TTR protein from forming amyloid deposits.
Drug status report:
- Vyndamax (tafamidis) – Has been approved by the FDA in the U.S. for the treatment of transthyretin amyloidosis cardiomyopathy (ATTR-CM). Tafamidis has also been approved in 41 countries outside of the U.S. to treat transthyretin amyloidosis polyneuropathy (ATTR-PN) – view factsheet
- Attruby (acoramidis) – Approved by the FDA for use in the U.S., Attruby is a TTR stabilizer developed for treating patients with transthyretin amyloidosis (ATTR) who have heart involvement (cardiomyopathy) – view factsheet
- Diflunisal – Approved in the U.S. by the FDA as a non-steroidal, anti-inflammatory drug (NSAID) that has shown to bind to the TTR protein in the blood and may thereby prevent the formation of amyloid.
Stopping production of TTR
The approach in stopping production of TTR proteins is through ‘gene silencing’. Novel treatments known as “gene silencers” have shown promising results in clinical studies. They prevent TTR protein production by blocking the TTR gene. These treatments have been approved and are currently available for use for hATTR peripheral neuropathy, and Vutrisiran (Amvuttra) has been approved for use for hATTR cardiomyopathy.
Drug factsheets:
- Patisiran (Onpattro) — view factsheet
- Vutrisiran (Amvuttra) — view polyneuropathy factsheet | view cardiomyopathy factsheet
- Eplontersen (Wainua) — view factsheet
Removing amyloid deposits
There are currently no approved drugs aimed at removing amyloid deposits in hATTR.
Drug status report:
- Coramitug (PRX004) – Currently being tested in clinical trials.
Supportive treatment
Although they do not address the underlying cause, supportive treatments are important to help alleviate symptoms and improve quality of life. Overall, factors such as age, general health and extent of organ damage are taken into account when deciding on treatment.
Eligibility for Free Genetic Testing & Counseling
You may be eligible if you are an adult (18 and older) and:
- Have a diagnosis of ATTR amyloidosis
- Have symptoms of ATTR amyloidosis
- Have a family history of hATTR
How Can I Be Tested For Free?
Currently, there are two programs that offer the testing at no charge. They are sponsored by different drug companies, but both use Prevention Genetics as their testing provider. There is very little difference between them, and either is a good choice:
- Alnylam Act — Sponsored by Alnylam, available in US and Canada
- NavigATTR — Sponsored by AstraZeneca & Ionis, available in US
How Testing Works
Your healthcare provider can order the test. Any provider that ideally is familiar with you can place the order, including primary care physicians, nurse practitioners, cardiologists, orthopedic surgeons, and other specialists.
The test will be conducted at your provider’s office, where they will take a blood sample (preferred), or collect saliva or buccal (cheek) cells. Results usually come back in 3 weeks. You will be offered free genetic counseling through Genome Medical before testing and after to help you understand your results and the next steps.
Download Genetic Testing Info to Print Out →
In this video, learn more information about hereditary ATTR amyloidosis treatments from Dr. James Ampadu.
You can download the slides from Dr. Ampadu’s video above by clicking here.
My Amyloidosis Pathfinder
Find, compare, and contact the treatment centers that fit your personal needs with ARC’s online My Amyloidosis Pathfinder (MAP) tool. Your personalized MAP profile will connect you to the centers and clinical trials that match what you’re looking for.
Additional Support
Finding the right support is important to help you manage your care. Talking to people who listen and answer your questions is a key part of feeling well. At ARC, we’re here to provide resources and information to guide you on your journey—you don’t have to face this alone. There are also many support groups around the world where you can connect with others who understand. Find a support group and find out more about our PEER Link program.
