AMYLOIDOSIS

Understanding Hereditary ATTR Amyloidosis

Hereditary ATTR (hATTR) amyloidosis is an inherited, progressive disease caused by a genetic mutation that results in the misfolding of transthyretin (TTR) proteins. This results in the formation of amyloid fibrils that could deposit in the nerves, heart, and/or gastrointestinal (GI) tract.

hATTR amyloidosis affects approximately 50,000 people worldwide. Many people remain undiagnosed or misdiagnosed.

hATTR Amyloidosis

Due to the gene variant in people with hATTR amyloidosis, the TTR protein, which is made primarily in the liver and carries vitamin A, can undergo a change from its normal function. The abnormal protein then accumulates throughout the body as amyloid fibrils—particularly in the heart, nerves, GI tract, and musculoskeletal tissues—causing debilitating symptoms.

hATTR amyloidosis is an autosomal dominant disease, meaning a person needs only one copy of the variant gene to manifest the disease. Therefore, it can be inherited from one parent. More than 120 different TTR gene variants have been identified to cause hATTR amyloidosis. Some variants are more common in certain populations, including those of Portuguese, Swedish, Japanese, African and Irish descent.

Symptoms Associated with hATTR Amyloidosis

hATTR amyloidosis symptoms can vary from person to person, depending on which organs or tissues are affected, and can worsen as the disease progresses.

Symptoms may include:

Numbness, pain and weakness in the limbs
Impaired balance and difficulty walking, and musculoskeletal manifestations, such as carpal tunnel syndrome and osteoarthritis

Alternating episodes of diarrhea, constipation, nausea, and vomiting

Cardiovascular issues, such as shortness of breath, conduction abnormalities and arrhythmias

For a more comprehensive list of symptoms, see the hATTR amyloidosis backgrounder below.

Learn More About hATTR Amyloidosis

Download the Alnylam hATTR amyloidosis Backgrounder.

Download

This is one family’s story

“Amyloidosis has kind of been the black cloud over my family.” – Tonya, family living with hATTR amyloidosis

References

Gertz MA, Benson MD, Dyck PJ, et al. J Am Coll Cardiol. 2015;66(21):2451-2466.
Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.
Plante-Bordeneuve V. J Neurol. 2014;261(6):1227-1233.
Hanna M. Curr Heart Fail Rep. 2014;11(1):50-57.
Damy T, Judge DP, Kristen AV, et al. J Cardiovasc Transl Res. 2015;8(2):117-127.
Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
Mohty D, Damy T, Cosnay P, et al. Arch Cardiovasc Dis. 2013;106(10):528-540.
Sekijima Y, Yoshida K, Tokuda T, Ikeda S. 2001 Nov 5 [Updated 2021 July 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2022. https://www.ncbi.nlm.nih.gov/books/NBK1194/.
Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
Rowczenio DM, Noor I, Gillmore JD, et al. Hum Mutat. 2014;35:E2403-E2412.
Dungu JN, Anderson LJ, Whelan CJ, Hawkins PN. Heart. 2012;98:1546-1554.
Aus dem Siepen F, Hein S, Prestel S, et al. Clin Res Cardiol. 2019;108:1324-1330.
Data on file. Alnylam Pharmaceuticals, Inc.

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