Early Diagnosis Crucial For Hereditary ATTR Amyloidosis
A disease called hereditary ATTR amyloidosis (hATTR) is linked to a genetic mutation that has been passed through generations of Americans with ancestors from West African countries such as Ghana, Sierra Leone, Cote d’Ivoire and Nigeria.1 Hereditary ATTR amyloidosis is difficult to diagnose and often missed by doctors and patients because its symptoms and related complications, which include numbness, tingling or loss of sensation in the hands and feet, dizziness, and fainting, are similar to those of common conditions, such as diabetes and hypertension (high blood pressure). But unlike these conditions, which are frequently recognized and can be managed through a combination of lifestyle factors and a variety of available medicines, hereditary ATTR amyloidosis is a complex, multi-symptom disease that worsens over time if not addressed. Today, accurate genetic tests that diagnose hereditary ATTR amyloidosis are readily available, so early action is important.
In people with hereditary ATTR amyloidosis, a protein called TTR is formed abnormally, resulting in a substance called amyloid building up in multiple organs and tissues of the body. This amyloid buildup causes organs to stop working normally. Genetic studies have indicated that West African ancestry is the most highly represented ethnicity among African Americans, and the inherited genetic mutation is as common in the United States as it is in West Africa.2,3,4
Families of West African descent that carry the genetic mutation often have generations of relatives with unexplained heart problems. Research shows that non-heart related symptoms can also occur in hereditary ATTR amyloidosis patients with West African ancestry, including carpal tunnel syndrome.5
Len S., a hereditary ATTR amyloidosis patient, experiences symptoms of polyneuropathy, including significant pain in his hands and feet. This has impacted his ability to perform daily tasks, such as buttoning a shirt, maintaining a steady step while walking, and gripping onto items. He also suffers from diarrhea, a result of damage to the nerves that control the small intestine.
“When I was diagnosed with hereditary ATTR amyloidosis, I was alarmed because I had been taking care of myself and working out every day,” said Len. “Polyneuropathy greatly impacts my active lifestyle. I also enjoy traveling with my wife, and this interferes with our travels.”
As polyneuropathy progresses, the impact can become more severe, leading to changes in balance and coordination, pain in the joints, and digestive problems. This often leaves hereditary ATTR amyloidosis patients unable to drive, dress themselves, work, or move around without a cane or wheelchair. Those with advanced symptoms may require help from a caregiver to perform basic daily tasks like using the bathroom, and in many cases, patients become bedbound and cut off from the outside world.
“It is important to be aware of and pay attention to the mix of symptoms patients may be experiencing that are potential signs of hereditary ATTR amyloidosis,” said Ola Akinboboye, M.D., medical director at Queens Heart Institute in Rosedale, N.Y., and Clinical Associate Professor of Medicine at New York University. “For example, being attuned to signs of polyneuropathy, which may present earlier in the progression of hereditary ATTR amyloidosis than heart problems, should help physicians and patients recognize the condition sooner and confirm diagnosis faster.
Another way to help recognize hereditary ATTR amyloidosis sooner is for doctors to know and understand their patient’s family history. For example, letting your doctor know if neuropathy runs in your family, or if someone in your family has passed away from unexplained heart problems, can trigger additional discussions and lead to faster diagnosis.
“I started talking to my doctor about my family medical history when I saw my mother’s medical records,” said Len. “The word ‘amyloidosis’ was in the records but I didn’t know what it meant, and no one in my family knew about it. Telling my doctor about my mother’s illness was instrumental in getting to the bottom of my own hereditary ATTR amyloidosis diagnosis.”
Hereditary ATTR amyloidosis is an autosomal dominant genetic disease, meaning that every first-degree relative of an affected patient — every parent, sibling, or child — has a 50% chance of having the same gene mutation. The hereditary nature of the disease means that those living with hereditary ATTR amyloidosis often suffer the dual burden of watching older loved ones suffer with the disease. “TTR amyloidosis can be detected through either an imaging scan or biopsy. But a genetic test is the only way to confirm that the amyloid is due to the hereditary (genetic) form of the disease,” said Dr. Akinboboye.
Those who think they are experiencing symptoms of hereditary ATTR amyloidosis, should talk to their doctor for further evaluation, which may include genetic testing. Genetic testing, which is available through no-cost, confidential programs such as hATTR Compass, is the only way to confirm if patients have hereditary ATTR amyloidosis. Hereditary ATTR Compass provides genetic counseling and support throughout the genetic testing process for patients and their families. Now, with the introduction of treatments, it’s crucial to recognize the signs and signals of the disease earlier. There are different treatment options available to address different symptoms of hereditary ATTR amyloidosis, including neuropathy symptoms. Physicians can determine what treatment may be appropriate for their patient.
Though he understands that it can be scary or uncomfortable, Dr. Akinboboye suggests patients have open and candid conversations with their doctors about their symptoms, no matter how minor they may seem, speaking up if current treatments are not working and symptoms are progressing, and getting to know more about their family’s medical history.
“Even if what you’re feeling doesn’t feel like a big deal to you — for example feeling more tired than usual during or after exercise or feeling dizzy or short of breath from time to time — it’s important to share this information with your doctor so that they can build a full picture of your health,” adds Dr. Akinboboye.
Today, Len is working with his doctor to manage the disease. “It’s important to be your own best advocate – arm yourself with as much information as possible and bring that information to your doctor so you can sort through and understand what is correct and what is misinformation,” he said. “And, above all, take care of yourself and stay positive.”
Dr. Akinboboye urges other doctors to become more aware of and familiar with hereditary ATTR amyloidosis. “Physicians are in a position to change patient lives and address an illness that may have affected families for generations,” says Dr. Akinboboye. “There’s no time like the present to make a real difference for the future.”
©2019. Akcea Therapeutics, Inc. All rights reserved. US-TTR-XXXXXXX 12/19
 Jacobson DR, Alexander AA, Tagoe C, et al. The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. Mol Genet Genomic Med. 2016;4(5):548–556. Published 2016 Jul 14. doi:10.1002/mgg3.231
 Tishkoff, S., et al. The Genetic Structure and History of Africans and African Americans. Science. 2009;324(5930):10351044. doi:10.1126/science.1172257
 Jacobson, D., et al. Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African– Americans. Amyloid. 2015;22(3): 171174. doi: 10.3109/13506129.2015.1051219\
 Jacobson, D., et al. The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. Molecular Genetics & Genomic Medicine. 2016;4(5):548556. doi: 10.1002/mgg3.231
 Connors, L. et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009;158(4):607614. https://doi.org/10.1016/j.ahj.2009.08.006
© 2020. Akcea Therapeutics, Inc. All rights reserved. US-TTR-2000009 2/20