Hereditary Transthyretin Amyloidosis (hATTR) is a rare condition caused by one or more changes in your genes for a protein called Transthyretin (TTR). These changes lead to a build-up of abnormal proteins called amyloid in different parts of the body including tissues and organs. As the disease progresses it typically presents as heart and/or nerve issues otherwise called cardiomyopathy (CM) or polyneuropathy (PN). The accumulation of this protein in tissues can also lead to additional symptoms like carpal tunnel, movement issues, nerve pain, vision changes, and heart failure. Patients that experience hATTR with polyneuropathy can eventually have trouble with movements of the arms or legs while patients with cardiomyopathy can experience fatigue, abnormal heart rhythms and shortness of breath. Since this disease causes a progressive worsening in symptoms as well as health-related quality of life, early detection and treatment is important otherwise permanent complications can occur. It is estimated that about 1 in every 100,000 people in the United States have the condition, with African American males being affected the most. Symptoms typically start after the age of 50 but can begin anywhere between the ages 20 and 80.
Rare Disorders
ONPATTRO™
To treat polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults.
Contact PANTHERx Rare
-
1-833-432-7275
Contact the Manufacturer
-
Alnylam
-
-
1-833-432-7275
PANTHERx Rare & Manufacturer Resources:
Symptoms
- Heart disease: Shortness of breath, chest pain, weakness, swelling at ankles, fainting, and abnormal heart rhythm.
- Nerve issues: Carpal tunnel (in both hands), tingling and numbness in feet and legs, difficulty walking or hand movements, becoming lightheaded when standing, trouble urinating, and sexual difficulties.
- Stomach problems: Upset stomach, vomiting, loose stool, weight loss, and stomach pain.
- Eyes: Vision loss or changes, dark floaters, extra blood vessels in the eye.
- Brain: Seizures, headache, memory loss, difficulty thinking clearly, stroke-like events.
Diagnosis and Testing:
Patients that have a family member with hATTR amyloidosis should receive genetic testing for the condition, since it can be passed down from a mother or father. Patients that have carpal tunnel in both hands, tingling or numbness in their legs, and/or issues moving around normally along with any of the previously mentioned symptoms above should see a specialist for evaluation.
Tests to detect hATTR amyloidosis may include:
- Testing tissue for amyloid presence.
- Testing for TTR specific protein in your blood.
- Genetic testing for the TTR gene.
Other tests are available to confirm if the heart is affected and include lab imaging, ECG to record the electrical signal in the heart, and blood work to look for specific heart proteins. The patient should also receive a full neurological exam to determine the level of the nerve issues they have been experiencing.
Treatment:
Unfortunately, no cure currently exists for hATTR Amyloidosis. Treatments today aim primarily to slow the condition from getting worse but do not remove the buildup of proteins causing the symptoms. A liver transplant may be an option for some patients to slow the worsening of this condition and symptoms linked with it as well as improve survival. Other medication therapies are available that can slow the worsening of the condition and improve symptoms like nerve or heart issues by stopping the production of amyloid protein and its buildup.
References
- 1) Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 8, 31 (2013). https://doi.org/10.1186/1750-1172-8-31
- 2) Lovley A, Raymond K, Guthrie SD, et al. Patient-reported burden of hereditary transthyretin amyloidosis on functioning and well-being. J Patient Rep Outcomes 5, 3 (2021). https://doi.org/10.1186/s41687-020-00273-y
- 3) Transthyretin Amyloidosis. Cleveland Clinic. Accessed October 23, 2022. Online at: https://my.clevelandclinic.org/health/diseases/17855-amyloidosis-attr
- 4) Hereditary ATTR Amyloidosis. Amyloidosis Research Consortium. Accessed October 23, 2022. Online at: https://arci.org/about-amyloidosis/hereditary-attr-amyloidosis
- 5) Coelho T, Ericzon BG, Falk R, et al. A guide to transthyretin amyloidosis. Amyloidosis Foundation. http://www.amyloidosis.org/wp-content/uploads/2017/05/2017-ATTR-guide.pdf
- 6) Conceição I, González-Duarte A, Obici L, et al. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21(1):5-9. doi:10.1111/jns.12153
- 7) Gertz MA. Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges. Am J Manag Care. 2017;23:-S0. https://www.ajmc.com/view/hereditary-attr-amyloidosis-burden-of-illness-and-diagnostic-challenges-article
- 8) Benson MD. Liver transplantation and transthyretin amyloidosis. Muscle & Nerve. 2012;47(2),157–162. https://doi.org/10.1002/mus.23521
- 9) Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. 2018;379(1):11-21. doi:10.1056/nejmoa1716153
- 10) Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. 2018;379(1):22-31. doi:10.1056/nejmoa1716793
- 11) Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial [published online ahead of print, 2022 Jul 23]. Amyloid. 2022;1-9. doi:10.1080/13506129.2022.2091985