Amyloidosis, hereditary, transthyretin-related

Hereditary transthyretin amyloidosis (or hATTR amyloidosis) can be very different from person to person. As such, it is difficult to make predictions about how the disease will progress for an individual. hATTR amyloidosis can potentially cause life-threatening complications and can lower life expectancy. However, improved surveillance techniques, which lead to prompt treatment of symptoms, has improved the outlook of this disorder in the last several years. There are several potential treatments being studied in clinical trials. Talk to your doctor and entire medical team about you or your family member's diagnosis and individual prognosis.

Some people with hATTR amyloidosis will ultimately need palliative or hospice care. Palliative care ensures that a dying person is as pain free as possible and that all their physical, social, emotional, and spiritual needs are met. Hospice care is a special institution that provides palliative care in an in-patient setting. Palliative and hospice care requires a close cooperation among family members, immediate relatives, and physicians, and other medical personnel. A primary care physician or local hospital may be able to offer advice and local resources for palliative care. Hospice care may also be recommended. A hospice is an institution that provides care for the chronically sick, particularly people who are terminally ill.

The National Hospice and Palliative Care Organization has specific information and support for families considering palliative or hospice care for a family member.

Taking care of someone with a long-term or chronic condition can be tiring and challenging and this is no different caregivers of people with hATTR amyloidosis. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at the Caregiver Action Network. This organization works to improve the quality of life for people who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. Support groups can also help provide support and advice for caregivers.

Support groups for hereditary transthyretin amyloidosis include the Amyloidosis Foundation and the Amyloidosis Support Groups.

General tips for caregivers from a psychologist with experience in the field can be found in a ThinkGenetic article here: https://news.thinkgenetic.com/2017/09/27/resilience-the-art-of-caregiving-preparing-for-curves-bumps-and-wrong-turns-by-adding-a-dose-of-resilience/.

Because children who have a parent with hATTR amyloidosis have a 50% chance of inheriting the gene change (mutation) that causes it, some wonder about whether their at-risk children should have genetic testing. However, many doctors caution that genetic testing should not be performed unless the child has developed symptoms (which is extremely rare, since symptoms usually happen in adults). Testing a child who does not show symptoms, sometimes called presymptomatic genetic testing, has drawbacks. There are also drawbacks in presymptomatic genetic testing in adult at risk for hATTR amyloidosis who does not show symptoms. There are many factors to consider before pursuing this option.

Genetic counselors can help a family learn about the option of genetic testing, including pros/cons and limitations. Discussion with a genetic counselor should happen before presymptomatic genetic testing should occur. In the U.S., you can find a genetic counselor near you by searching on the Find a Genetic Counselor website (from the National Society of Genetic Counselors) at http://www.nsgc.org/findageneticcounselor.

Following a healthy diet and getting proper nutrition is important for everyone, including people with hATTR amyloidosis. People should make an effort to eat right and have a balanced, healthy diet. Individuals with hATTR amyloidosis should talk to their medical team about eating right and proper nutrition. Sometimes, doctors may encourage people to modify their diet. For example, a low-salt diet may be recommended to lower fluid retention, which can help people with hATTR amyloidosis who have heart or kidney involvement.

Hereditary transthyretin amyloidosis is caused by changes (mutations) to the TTR gene. These changes affect the protein (transthyretin) made by the gene. When proteins are formed, they are "folded" into a specific shape. Because of the change in the TTR gene, transthyretin is "misfolded" and is abnormally shaped. The misfolded proteins are called amyloid. Amyloid builds up in the body and damages surrounding tissues and organs. Some people are carriers of this disorder. This means that they have a change in the TTR gene, but do not have any symptoms. Some people never develop symptoms, while others may not develop symptoms until very late in life.

A genetic counselor can tell you much more about being a carrier of the condition, and symptoms that can happen. In the U.S., you can find a genetic counselor near you by searching on the Find a Genetic Counselor website (from the National Society of Genetic Counselors) at http://www.nsgc.org/findageneticcounselor.

The symptoms of hATTR amyloidosis can begin anywhere from the 20s to the 80s. hATTR amyloidosis is a genetic disorder. People have an altered gene called TTR that leads to an abnormal (misfolded) transthyretin protein. This misfolded and abnormally-shaped protein is called amyloid. These abnormal transthyretin proteins or amyloid are present in a person from birth, but they may not clump together to form amyloid deposits until later in life. This may be due, in part, to how people's chemical makeups in their bodies change as they age. The specific alteration (mutation) in the TTR gene can also influence when symptoms are most likely to start.

To find a medical professional nearby who can discuss information about gene changes in the TTR gene and the likely age of onset of symptom of hATTR amyloidosis a U.S. listing of medical geneticists can be found at the American College of Medical Geneticists website. In the U.S., you can find a genetic counselor near you by searching on the Find a Genetic Counselor website (from the National Society of Genetic Counselors) at http://www.nsgc.org/findageneticcounselor.

Hereditary transthyretin amyloidosis is caused by a change (mutation) in the TTR gene. This gene makes a protein called transthyretin. Because of the gene change, the transthyretin protein that is made is abnormally shaped. When proteins are formed, they are "folded" into a specific shape. Transthyretin is "misfolded" and is abnormally shaped. The misfolded proteins are called amyloid. The altered transthyretin, or amyloid, cannot perform its normal function. In addition, the misfolded proteins start to build up in tissues and organs of the body. The misfolded proteins will begin to merge together to form small or slender fibers called fibrils. When enough of the misfolded proteins (called amyloid) build up, they will damage the surrounding tissues and organs. The nerves, heart, kidneys, and gastrointestinal tract are commonly affected.

The medical cost of hATTR amyloidosis can be significant for some families, and some families may lack the resources necessary to provide for a chronically ill child. There are several organizations that provide financial assistance.

In the U.S.:

• The Social Security Administration provides disability benefits for people who qualify. Hereditary transthyretin amyloidosis is not listed in the publication called the Disability Evaluation Under Social Security, also called the "Blue Book." However, people with the disorder may still qualify for assistance if they have certain symptoms that qualify.
• The National Organization for Rare Disorders has links to organizations that can provide financial assistance.
• The National Human Genome Research Institute has extensive information on finding financial aid for medical treatment and services.

"Wild type" transthyretin amyloidosis is similar to the hereditary form. However, people with wild type transthyretin amyloidosis do not have a gene mutation (change) and the disorder is not inherited. Like hATTR amyloidosis, this disorder is caused by misfolding of the transthyretin protein. When proteins are formed, they are "folded" into a specific shape. Transthyretin is "misfolded" and is abnormally shaped. The misfolded proteins are called amyloid. The altered transthyretin, or amyloid, cannot perform its normal function. In addition, the misfolded proteins start to build up in tissues and organs of the body. The misfolded proteins will begin to merge together to form small or slender fibers called fibrils. When enough of the misfolded proteins (called amyloid) build up, they will damage the surrounding tissues and organs. The heart is most commonly affected in wild type transthyretin amyloidosis.

In hereditary transthyretin amyloidosis, this misfolding is cause by a genetic mutation (a change in a gene). In wild type transthyretin amyloidosis, the misfolding is not caused by a genetic mutation. Wild type transthyretin amyloidosis generally affects older men.

In groups where hATTR amyloidosis is more likely to occur something called genetic "anticipation'" may occur. Genetic anticipation is when a disorder becomes more severe and the onset of symptoms occur at an earlier age with each generation of a family.

A medical professional such as a genetic counselor or medical geneticist discuss details about genetic anticipation in hATTR amyloidosis. In the U.S., a listing of medical geneticists can be found at the American College of Medical Geneticists website. In the U.S., you can find a genetic counselor near you by searching on the Find a Genetic Counselor website (from the National Society of Genetic Counselors) at http://www.nsgc.org/findageneticcounselor.

There is a patient registry for hATTR amyloidosis. This is a database set up by researchers that contains information about patients with a particular disorder or group of disorders. This information helps researchers learn about a disorder, plan or study treatments, how a disorder progresses or affects people and other information. Patient registries require that patients either directly or through their doctor submit personal information. Talk to a genetic counselor about the pros or cons of participating in a patient registry.

As of September 2017, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is a study open to all physicians treating, and all individuals diagnosed with, or carrying a mutation that puts them at risk of transthyretin (TTR) amyloidosis.

The kidneys can be affected in hereditary transthyretin amyloidosis, but often no symptoms will develop. In rare instances, kidney damage can occur because of the buildup of transthyretin protein, called amyloid, that defines the disorder. The need for dialysis or a kidney transplant is possible in rare instances.

Hereditary transthyretin amyloidosis is caused by a change (mutation) in a gene called TTR. The protein made by this gene, called transthyretin, is unstable and becomes abnormally shaped. When proteins are formed, they are "folded" into a specific shape. Because of the change in the TTR gene, transthyretin is "misfolded." The misfolded proteins are called amyloid. In addition, the misfolded proteins start to build up in tissues and organs of the body. The misfolded proteins will begin to merge together to form small or slender fibers called fibrils. When enough of the misfolded proteins (called amyloid) build up, they will damage the surrounding tissues and organs. The nerves, heart, kidneys, and gastrointestinal tract are commonly affected.

Most transthyretin is made in the liver. The liver itself is not affected by the disease. Some people with hATTR amyloidosis may be candidates for a liver transplant because doctors believe the donor liver will make normal transthyretin. A liver transplant has been effective in treating certain people with this disorder, particularly people who have had disease symptoms for less than 5 years, are younger than 60 years old, have nerve disease limited to the lower legs or only have autonomic nerve involvement, and no significant problems with their hearts or kidneys. Liver transplants have not improved heart problems associated with hATTR amyloidosis and sometimes the nerve disease also does not improve. These transplants are not effective in people with leptomeningeal amyloidosis or familial oculoleptomeningeal amyloidosis. A liver transplant for hATTR amyloidosis is an effective treatment for certain people with this disorder.

Any type of transplant comes with both risks and benefits. Anyone considering this option should talk with the primary care physician and entire medical team to understand all aspects of the procedure. There are organizations that provide information on transplants. This includes the National Foundation for Transplants. The American Liver Foundation also provides information on liver transplants.

Diuretics (sometimes called "water pills") are commonly used to treat heart disease. Diuretics are medications that help to remove fluid from the body. These medications can help to relieve swelling that is caused by heart disease. However, the use of diuretics in hATTR amyloidosis is complicated. Although they can benefit a person by helping to management fluid levels, they can cause complications, particularly in people who also have kidney disease.

Talk to your doctor and entire medical team (including a heart specialist, a cardiologist) about your specific treatment plan.

The autonomic nervous system can be affected in people living with hereditary transthyretin amyloidosis. The autonomic nervous system controls actions of the body that occur without thinking about them. This means that these actions occur without a person's conscious thought about performing these actions. This includes regulating the heartbeat, sweating, the production of various fluids including tears and saliva, parts of the digestive process, and regulating body temperature.

Symptoms of autonomic nervous system dysfunction in hereditary transthyretin amyloidosis can include alternating bouts of diarrhea and constipation, a lack of sweating, a drop in blood pressure upon standing (orthostatic hypotension), and, in men, impotence.