Familial transthyretin amyloidosis

Title

Other Names:

Amyloidosis, hereditary, transthyretin-related; Transthyretin amyloidosis; Familial amyloid polyneuropathy; Amyloidosis, hereditary, transthyretin-related; Transthyretin amyloidosis; Familial amyloid polyneuropathy; Amyloidosis Transthyretin related; Transthyretin amyloid neuropathy; TTR amyloid neuropathy; Transthyretin amyloid polyneuropathy; Hereditary ATTR amyloidosis See More

Categories:

Nervous System Diseases

This disease is grouped under:

Amyloid neuropathy; Hereditary amyloidosis

Summary Summary

Familial transthyretin amyloidosis (FTA) is a rare inherited condition characterized by abnormal build-up of a protein called amyloid in the body's organs and tissues.^[1]^[2] Symptoms start in adulthood and get worse over time. Signs and symptoms depend on where the amyloid protein is building up.^[1] Amyloid build-up in the nerves of the peripheral nervous system causes a loss of sensation in the lower limbs, feet, and hands (peripheral neuropathy). Amyloid build-up can also affect the involuntary body functions, such as blood pressure, heart rate, and digestion.^[1]^[2] Other areas of the body that may be affected are the heart, kidneys, eyes, and gastrointestinal tract.^[1]

FTA is caused by changes (mutations) in the TTR gene. Inheritance is autosomal dominant, but not all people with a TTR gene mutation will develop FTA.^[2]^[3] Diagnosis of FTA is suspected by signs and symptoms and confirmed by tissue biopsy and genetic testing.^[1]

Primary treatment is a liver transplantation. This procedure removes the main source of amyloid from the body, but amyloid may still build-up in the heart, brain, and eyes. New medications have become available that block the formation of amyloid and may provide an alternative to liver transplant. Other treatments include heart and/or kidney transplantation, putting in a pacemaker, replacing the fluid in the eye (vitrectomy), and various medications.^[3] FTA is typically a fatal condition, but life expectancy depends on many factors.^[1]^[3]

Last updated: 11/15/2018

Symptoms Symptoms

Familial transthyretin amyloidosis (FTA) is a slowly progressing, adult-onset condition.^[1][13890] Symptoms depend on which body parts are most affected. The age symptoms begin may also vary by country. In Portugal and Japan, people with FTA usually start developing symptoms in their late 20s to 40s. In other parts of the world, people with FTA may not have symptoms until after age 50.^[2]

The most common form of FTA affects the peripheral nervous system. The peripheral nerves send messages from the brain and spinal cord to the rest of the body. Other forms of FTA can affect the brain, spinal cord, heart, and eyes.^[1]^[2]^[4]

Symptoms of FTA include^[5]

• Weakness, numbness or pain in the lower legs and feet
• Carpal tunnel syndrome in both wrists
• Sexual impotence
• Urinary problems, protein in the urine
• Diarrhea or constipation
• Unexplained weight loss
• Dry eyes, increased pressure in the eyes (glaucoma), seeing ‘floaters’
• Abnormal heart beat, enlarged heart
• Getting dizzy when moving from sitting to standing (orthostatic hypotension)
• Dry eyes and mouth

Later symptoms may include muscle weakness and stiffness, difficulty with coordination, stroke, seizures, dementia, and congestive heart failure.^[3]^[4]

Less common symptoms include skin changes, hearing loss, shortness of breath, and anemia.^[3]

Last updated: 11/15/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 31 |

Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Adult onset	Symptoms begin in adulthood	0003581
Amyloid deposition in the vitreous humor		0007841
Amyloidosis		0011034
Ataxia		0001251
Autosomal dominant inheritance		0000006
Cardiomegaly	Enlarged heart Increased heart size [ more ]	0001640
Cardiomyopathy	Disease of the heart muscle	0001638
Constipation		0002019
Constrictive median neuropathy		0012185
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Diarrhea	Watery stool	0002014
Dysarthria	Difficulty articulating speech	0001260
Headache	Headaches	0002315
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Hemiparesis	Weakness of one side of body	0001269
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Impotence	Difficulty getting a full erection Difficulty getting an erection Erectile dysfunction [ more ]	0000802
Increased CSF protein		0002922
Muscle weakness	Muscular weakness	0001324
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Orthostatic hypotension due to autonomic dysfunction		0004926
Paraplegia	Leg paralysis	0010550
Peripheral axonal neuropathy		0003477
Polyneuropathy	Peripheral nerve disease	0001271
Progressive	Worsens with time	0003676
Seizures	Seizure	0001250
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Stroke-like episode	Stroke-like episodes	0002401
Tremor	Tremors	0001337
Urinary incontinence	Loss of bladder control	0000020
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505

Showing of 31 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

Cause Cause

Familial transthyretin amyloidosis (FTA) is caused by changes (mutations) in the TTR gene. This gene is responsible for making a protein called transthyretin which transports vitamin A and a hormone called thyroxin to many parts of the body. Mutations in TTR lead to a transthyretin protein that is not made correctly. The faulty protein then folds up to form amyloid. Amyloid builds up in various parts of the body causing nerve and tissue damage.^[4]

Most people who have FTA have inherited the TTR mutation from a family member. However, a few people with FTA will have no family history of the disease and have a new (de novo) mutation in the TTR gene.^[1]^[4]

Last updated: 11/15/2018

Inheritance Inheritance

Familial transthyretin amyloidosis (FTA) is inherited in families in an autosomal dominant pattern. This means only one copy of a mutated TTR gene is needed for a person to have the condition. The mutation can be inherited from a parent or can happen by chance for the first time (de novo) in an individual.^[4]

Each child of a person with FTA has a 50% chance of inheriting the mutation. Most children who inherit a TTR mutation will develop FTA, although they could be more or less severely affected than their parent. For reasons that are unclear, some people have mutations in the TTR gene and never develop FTA.^[4]

Last updated: 11/15/2018

Diagnosis Diagnosis

The diagnosis of familial transthyretin amyloidosis (FTA) can be difficult because the signs and symptoms of FTA often look like other, more common conditions. Doctors and nurses use a combination of signs and symptoms and laboratory and genetic tests to determine if someone has FTA. Laboratory tests include examination of a biopsy of an affected area, along with genetic testing to look for a mutation in TTR gene.^[3]^[4]

Last updated: 11/15/2018

Treatment Treatment

There is no treatment available for familial transthyretin amyloidosis (FTA) that reverses damage caused by amyloid deposits, but there are treatments that may prevent or delay progression.^[1]^[3] Treatment depends on which tissues are affected and how far the disease has progressed.^[3]

Liver transplantation is the "gold standard" for treatment for FTA, because it replaces the main source of amyloid. It may slow or halt progression of peripheral neuropathy, but the disease often still progresses in the eyes and brain. Transplantation ideally should be done as early as possible before there are severe neurological problems.^[1]

Several medications have been developed that slow the build-up of amyloid along nerves and in other parts of the body. These include tafamidis, diflunsial, and more recently inotersen and patisiran. There are other drugs that are currently under investigation for this condition.^[3]^[6]

Additional treatments may include heart and/or kidney transplantation, replacement of the liquid part of the eye (vitrectomy) for eye involvement, and carpal tunnel surgery.^[3]

Diuretics, medications that remove excess water and salt from the body, are often used to manage congestive heart failure associated with the disease. Other symptoms of FTA are treated as they arise.^[3]

Last updated: 11/15/2018

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Patisiran (Brand name: Onpattro) - Manufactured by Alnylam Pharmaceuticals, Inc.
FDA-approved indication: August 2018, patisiran (Onpattro) was approved for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
National Library of Medicine Drug Information Portal
Inotersen (Brand name: Tegsedi) - Manufactured by Ionis Pharmaceuticals, Inc.
FDA-approved indication: October 2018, inotersen (Tegsedi) was approved for the treatment of the polyneuropathy of hereditary transthyretinmediated amyloidosis in adults.
National Library of Medicine Drug Information Portal

Prognosis Prognosis

The outlook and life expectancy for each person with familial transthyretin amyloidosis (FTA) varies and depends on the TTR gene mutation present, organ(s) involved, and how early a person is diagnosed and treated. Some people whose symptoms begin at a younger age may live for only a few years after diagnosis, while older patients with slowly progressive disease can live for many years.^[1]^[3] On average, people with FTA typically live for 7-12 years after they are first diagnosed.^[3]

The long-term outlook after liver transplant is also influenced by many factors, including the type of amyloid present, nutritional status, age, and how much the brain and heart are involved.^[7] Newer medications are now available that help slow the build-up of amyloid and delay symptoms and it is not yet clear how these medications will affect the long-term outlook for people with FTA. People with questions about their personal outlook should speak with their healthcare providers.

Last updated: 11/15/2018

Statistics Statistics

The exact incidence of familial transthyretin amyloidosis is unknown. It is more common in certain parts of Portugal, Sweden, and Japan. The common TTR gene mutation, known as Val30Met, associated with familial transthyretin amyloidosis (FTA) occurs in about 1 in 583 people in some parts of Portugal, compared to about 1 in 100,000 people in the US. A different TTR gene mutation associated with FTA, Val122Ile, is more common in parts of West Africa. ^[2]^[4] While FTA is more common in certain parts of the world, it has been found across all ethnic groups and occurs equally in males and females.

Last updated: 11/15/2018

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Familial transthyretin amyloidosis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Amyloidosis Australia, Inc.
131-133 Napier Street
St. Arnaud,
Victoria, 3478
Australia
Telephone: 03 5495 1169
E-mail: info@amyloidosis.com.au
Website: http://www.amyloidosis.com.au/
Amyloidosis Foundation
7151 N. Main Street
Suite 2
Clarkston, MI 48346
Toll-free: 877-AMYLOID (1-877-269-5643)
E-mail: info@amyloidosis.org
Website: http://www.amyloidosis.org/
Amyloidosis Support Groups Inc.
232 Orchard Drive
Wood Dale, IL 60191
Toll-free: 866-404-7539
Telephone: 847-350-7540
E-mail: info@amyloidosissupport.com
Website: http://www.amyloidosissupport.com

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Amyloidosis Awareness is an illustrated booklet for patients and physicians developed by Amyloidosis Support Groups Inc. Versions of the booklet are also available in Spanish and Portuguese.
Genetics Home Reference (GHR) contains information on Familial transthyretin amyloidosis. This website is maintained by the National Library of Medicine.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
PubMed is a searchable database of medical literature and lists journal articles that discuss Familial transthyretin amyloidosis. Click on the link to view a sample search on this topic.

News & Events News & Events

News

The XVIth International Symposium on Amyloidosis
May 31, 2017

GARD Answers GARD Answers

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I am living in Israel, and my father has the rare disease familial amyloid polyneuropathy. What are the treatment options for this disease? Have people been successfully treated? See answer

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References References

Roberts JR. Transthyretin-Related Amyloidosis. Medscape Reference. Updated 10/10/2018; https://emedicine.medscape.com/article/335301-overview.
Transthyretin amyloidosis. Genetics Home Reference. Updated 10/30/2018; https://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis.
Ando Y, Coelho T, Berk JL. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet Journal of Rare Diseases. 2013; 8(31):https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-31.
Sekijima Y, Yoshida K, Tokuda T, Ikeda S-I. Familial transthyretin amyloidosis. GeneReviews. Updated January 26, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1194/. Accessed 11/15/2018.
Pinto MV, Barreria AA, Bulle AS, Gomes de Freitas MR, et al. Brazilian consensus for diagnosis, management and treatment for transthyretin familial amyloid polyneuropathy. Arg Neuropsiquiatr. Sep 2018; 76(9):609-621. https://www.ncbi.nlm.nih.gov/pubmed/30365625.
Obici L, Kuks JB, Buades J, et al. Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis. Curr Opin Neurol. February, 2016; Suppl 1:S27-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739313/.
Plante-Bordeneuve V. Transthyretin familial amyloid polyneuropathy: an update. Jl of Neuro. 2018; 265:976-983. https://www.ncbi.nih.gov/pubmed/29249054.