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

Summary Summary

Familial transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. Amyloid deposits in the nerves of the peripheral nervous system result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system (which controls involuntary body functions such as blood pressure, heart rate, and digestion) as well as the central nervous system (brain and spinal cord) may also be affected. Other areas of the body affected include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms develop varies widely among affected individuals, and may be between ages 20 and 70 years. Mutations in the TTR gene cause the condition. Although it is inherited in an autosomal dominant pattern, not all people who have a TTR gene mutation will develop familial transthyretin amyloidosis.^[1]

There are three major forms of familial transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.^[1] The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. The leptomeningeal form of transthyretin amyloidosis primarily affects the central nervous system. The cardiac form of transthyretin amyloidosis affects the heart.^[1] To read more about the different forms of familial transthyretin amyloidosis, click here.

Last updated: 7/1/2011

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Adult onset	-
Amyloid deposition in the vitreous humor	-
Amyloidosis	-
Ataxia	-
Autosomal dominant inheritance	-
Cardiomegaly	-
Cardiomyopathy	-
Constipation	-
Dementia	-
Diarrhea	-
Dysarthria	-
Dysautonomia	-
Headache	-
Hearing impairment	-
Hemiparesis	-
Hyporeflexia	-
Impotence	-
Increased CSF protein	-
Nystagmus	-
Orthostatic hypotension due to autonomic dysfunction	-
Paraplegia	-
Peripheral axonal neuropathy	-
Phenotypic variability	-
Polyneuropathy	-
Progressive	-
Seizures	-
Spasticity	-
Stroke-like episode	-
Tremor	-
Urinary incontinence	-
Visual impairment	-

Last updated: 9/1/2017

Treatment Treatment

There have been several recommendations proposed for evaluating and treating individuals with familial transthyretin amyloidosis.^[2] To establish the extent of the disease in a newly diagnosed individual, evaluation may include:

Complete neurologic assessment including baseline nerve conduction studies (which measure the speed at which nerves conduct impulses)
Evaluation of the heart for cardiomyopathy and to evaluate amyloid deposition in the heart
Gadolinium-enhanced MRI of the brain and spinal cord to evaluate central nervous system (CNS) amyloidosis
Ophthalmologic (eye) evaluation
Evaluation of renal function^[2]

Treatment for familial amyloid polyneuropathy may include:

Carpal tunnel release surgery for carpal tunnel syndrome
Vitrectomy for vitreous involvement^[2]

In terms of preventing some signs and symptoms associated with the condition, orthotopic liver transplantation (OLTX) is reportedly the only effective therapy for the neuropathy associated with familial transthyretin (TTR) amyloidosis. This type of liver transplantation involves replacing the recipient liver with a donor liver. This procedure removes the main production site of the abnormal protein. Successful OLTX results in rapid disappearance of the harmful protein and thus stops the progression of neuropathy. It has been recommended that individuals with the condition considering OLTX be at an age younger than 60 years; have a disease duration less than five years; have either polyneuropathy that is restricted to the lower extremities (legs) or autonomic neuropathy alone; and have no significant cardiac (heart) or renal (kidney) dysfunction. OLTX is reportedly not effective in the non-neuropathic forms of familial transthyretin amyloidosis (i.e., cardiac amyloidosis, leptomeningeal amyloidosis, and familial oculoleptomeningeal amyloidosis). Individuals with leptomeningeal involvement may not be candidates for liver transplantation.^[2]

Last updated: 7/1/2011

Management Guidelines

The Amyloid Treatment and Research Program at Boston University School of Medicine provides information on the treatment of different forms of amyloidosis.
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.
The NORD Physician Guide for Familial transthyretin amyloidosis was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.

Prognosis Prognosis

The prognosis for individuals with transthyretin amyloidosis depends on the presence and type of transthyretin protein being deposited, as well as the organ(s) affected by the disease. Patients with early-onset disease and certain types of transthyretin protein may die within a few years of diagnosis, while older patients with slowly progressive disease can live for decades after the onset of symptoms and may never develop life-threatening disease. Unlike in other types of amyloidosis, symptomatic cardiac involvement does not necessarily mean a poor prognosis.^[3]

Last updated: 7/1/2011

Do you have updated information on this condition? Let us know.

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 studying or have studied 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 9001 9312
E-mail: ellen@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 , muriel@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? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

The Mayo Clinic provides information on the diagnosis and treatment of amyloidosis.
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

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

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017
The XVIth International Symposium on Amyloidosis
May 31, 2017

NCATS Co-Sponsored Conferences

XIV International Symposium on Amyloidosis Sunday, April 27, 2014 - Friday, May 2, 2014
Location: Indianapolis, Indiana
Description: One important goal is to foster interactions between investigators who do not meet regularly outside of this event. Through this conference, experts can share unpublished scientific and clinical information about rare diseases that are hard to treat. A second crucial goal is to stimulate interest in a new generation of investigators by providing generous support for at least 10 junior-level researchers to attend the meeting, giving out awards for the most promising clinical research, the best poster, and the best oral presentation by young investigators, and providing childcare options.

Contact: Rebekah S. Rasooly, Ph.D.(301) 594-6007rrl85i@nih.gov

Co-funding Institute(s): National Institute of Diabetes and Digestive and Kidney Diseases, Office of Rare Diseases Research

Related Diseases Related Diseases

The following diseases are related to Familial transthyretin amyloidosis. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

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

Transthyretin amyloidosis. Genetics Home Reference (GHR). 2009; http://ghr.nlm.nih.gov/condition/transthyretin-amyloidosis. Accessed 7/15/2010.
Yoshiki Sekijima, Kunihiro Yoshida, Takahiko Tokuda, Shu-ichi Ikeda. Familial transthyretin amyloidosis. GeneReviews. September 15, 2009; http://www.ncbi.nlm.nih.gov/books/NBK1194/. Accessed 6/29/2011.
Jefferson R Roberts. Amyloidosis, Transthyretin-related. eMedicine. September 15, 2009; http://emedicine.medscape.com/article/335301-followup#a2650. Accessed 6/29/2011.

Do you know of a review article? Send us your suggestions.