Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
Hereditary transthyretin amyloidosis (hATTR) is a rare genetic disease in which protein amyloid accumulates in several organs and tissues of the body.1 Depending on which organ is affected, patients can present with different signs and symptoms. Most commonly, hATTR can greatly affect the nerves of the peripheral nervous system, leading to numbness of the hands, feet, and legs, and it can also affect the heart, with patients presenting with signs of both polyneuropathy and cardiomyopathy.1,2 If left untreated, hATTR can lead to complications that are life-threatening.3
Identifying Signs of Hereditary Transthyretin Amyloidosis
As a systemic and progressive disease, hATTR can affect not only nerves and the heart, but also many other organs and tissues.3,4 Patients can experience a range of nonspecific symptoms that may prompt clinicians to diagnose other diseases rather than hATTR. A delay in appropriate treatment can follow a delayed diagnosis.
In addition to pain, numbness, tingling, and weakness in the body (polyneuropathy) and cardiomyopathy, clinical signs of hATTR that patients should pay attention to include orthostatic hypotension, urinary tract infections, sexual dysfunction, abnormal sweating, arrythmia, congestive heart failure, dizziness, fatigue, swelling in the legs, kidney failure, nausea, vomiting, diarrhea or constipation, and ocular problems like glaucoma.3
There are many symptoms of hATTR that both patients and clinicians need to be aware of. These include progressive neuropathy on both sides of the body and at least 1 of the following symptoms: signs of early autonomic dysfunction (such as dry mouth or incontinence), symptoms of heart failure (such as fatigue or edema), severe and chronic diarrhea or constipation, unexplained weight loss, bilateral carpal tunnel syndrome, and ocular problems such as floaters/vitreous opacities.3 Health care provided to these patients should be coordinated between different specialists, including neurologists, cardiologists, and ophthalmologists.4
Inheritance of Hereditary Transthyretin Amyloidosis
Hereditary transthyretin amyloidosis is an inherited, autosomal dominant condition driven by mutations in the transthyretin (TTR) gene. Many different TTR mutations have been identified.1-3 Patients may consider a consultation with a genetic counselor to better understand the implications of the genetics of the disease and how it may affect their families. Immediate family members of patients, such as parents or siblings, should consider genetic testing, as they are at a higher risk of developing hATTR.5 Knowing if there is a family history of hATTR can be also helpful for achieving a diagnosis. Patients should be made aware that despite carrying a specific variant of the disease, symptoms and disease progression can vary among family members, making it difficult to predict how the disease will evolve. Genetic testing may also carry emotional or social consequences that patients can work through with a genetic counselor.3
Seeking Information and Support
There are several groups and organizations around the world that can not only work as a source of up-to-date information about hATTR, but can also provide support to patients with hATTR and their families by connecting them to others sharing the same condition.
The Amyloidosis Foundation is a nonprofit organization in the United States that prioritizes awareness of the disease and early diagnosis while providing patients with information. This organization also prioritizes the education of professionals through research grants and medical conferences.6
The Amyloidosis Research Consortium (ARC) is a nonprofit organization focused on developing awareness and treatment options for amyloid diseases, aiming to help prolong the lives of people affected by these diseases.3,7 Their activity includes collaborations with the government, industry, and academia, and their outreach activities are designed for patients and their families, caregivers, clinicians, and researchers.7 The ARC has made several resources available that are intended to be a guide for helping patients make informed decisions on their disease and to shed light on how the disease can be managed.8
The Amyloidosis Support Groups website provides instant information on groups that are located in the United States,9 and there are also public and private Facebook groups in which patients may participate. These include Amyloidosis International, Amyloidosis ATTRv (hATTR)-Hereditary-FAP-FAC, and Amyloidosis Awareness.10-12 Other groups and organizations are scattered around the world in countries such as Australia, Brazil, Canada, France, Portugal, and the United Kingdom.8
1. Familial transthyretin amyloidosis. Genetic and Rare Diseases Information Center (GARD). Updated November 8, 2021. Accessed July 25, 2022.
2. Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M. Diagnosis and treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy: current perspectives on improving patient care. Ther Clin Risk Manag. 2020;16:109-123. doi:10.2147/TCRM.S219979
3. Disease overview: hereditary transthyretin amyloidosis. Amyloidosis Research Consortium (ARC). Accessed July 25, 2022.
4. Adams D, Algalarrondo V, Polydefkis M, Sarswat N, Slama MS, Nativi-Nicolau J. Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression. Orphanet J Rare Dis. 2021;16(1):411. doi:10.1186/s13023-021-01960-9
5. Genetic testing and counseling for hATTR amyloidosis. American Heart Association. Accessed July 25, 2022.
6. Amyloidosis Foundation homepage. Amyloidosis Foundation. Accessed July 25, 2022.
7. Amyloidosis Research Consortium homepage. Amyloidosis Research Consortium (ARC). Accessed July 25, 2022.
8. Finding support. Amyloidosis Research Consortium (ARC). Accessed July 25, 2022.
9. Amyloidosis support groups. Amyloidosis Support Groups. Accessed July 25, 2022.
10. Amyloidosis International Facebook group. Facebook. Accessed July 25, 2022.
11. Amyloidosis ATTRv (hATTR)-Hereditary-FAP-FAC Facebook group. Facebook. Accessed July 25, 2022.
12. Amyloidosis Awareness Facebook group. Facebook. Accessed July 25, 2022.
Reviewed by Harshi Dhingra, MD, on 7/21/2022.