We Have What? hATTR Amyloidosis: My Family’s Journey
Every so often an opinion poll goes around on social media asking if folks would want to know in advance if they carry genetic material that could cause a fatal disease. Most people say no. Some of these diseases are terrifying, and advanced knowledge about something for which there is no cure? No thanks.
I’ve been a health reporter for years and know full well that early detection is crucial. But I’ve never taken any of these polls. Honestly, I’ve never felt the need.
That stance was called into question when my mom contracted pneumonia.
While in the hospital being treated, her medical team noticed fluid buildup caused by a leaking valve. A cardiac catheterization showed no blockage in her arteries (“she has the arteries of a 17-year-old,” one cardiologist said in amazement). A trans-esophageal echocardiogram was equally uninformative. Yes, her mitral valve was leaking. No, they didn’t know why.
But maybe she was a candidate for a relatively new procedure to repair the valve. If so, she’d be good as new. To prepare for the new procedure, she needed an MRI.
The MRI showed Mom’s heart muscle was thicker than it should be. This led to a heart biopsy. And finally, a diagnosis: something called amyloidosis. My mom struggled to pronounce it for a while. It could cause heart failure, they said.
We learned that there are several types of amyloidosis, so we needed to find out which type of amyloidosis she had. There is light chain amyloidosis, which sounded suspiciously akin to a blood cancer to my health journalist’s ears. I couldn’t get a straight answer about this, even when the recommended therapy for this type of amyloidosis included chemotherapy. There was wild-type ATTR amyloidosis, which the doctors said typically occurred later in life. And hereditary ATTR (hATTR) amyloidosis, a genetic and rare form of the disease that affects about 50,000 people worldwide with about 3-4% of African Americans carrying a TTR gene variant (i.e., mutation) called Val122Ile.
There were a lot of tests involved to determine which kind of amyloidosis she had. One night she had to produce nine huge tubes of blood. Then there was the three-gallon jug to collect a week’s worth of urine; this was to test Mom’s kidneys. She was also scheduled to have a bone marrow biopsy and a body X-ray.
There were also lots of questions about family history. Both my maternal grandparents suffered from congestive heart failure (CHF). My grandmother, who passed away at age 76, had diabetes, and though the link between diabetes and heart disease wasn’t discussed with her during her lifetime, CHF was listed as the cause of death on her death certificate. Granddaddy, once a smoker, battled emphysema and CHF the last two years of his life. Though he’d quit smoking before I was born, and had been nicotine free for nearly 40 years, his tobacco habit exacted a high price in the end. When he died at age 85, there’d been no mention of amyloidosis.
Knowing Family Medical History Is Key
While we waited for test results, a genetic counselor charted our family medical tree as best as she could. But as in many African American families, figuring out the tangled branches is a tall order. Even before being diagnosed with a disease we’d never heard of, there were gigantic holes in our family health history.
There’s the great-aunt who blamed her daughter’s death from asthma on a blister. High blood pressure and diabetes had run roughshod through generations of relatives, but nobody talked about the connection to heart disease. Scads of ancestors died without ever sharing their diagnoses. And this is all without taking into account the limitations 400 years of slavery and the difficulty African American families have in gathering complete medical knowledge.
Fortunately, blood test results solved the four-month-long mystery. My mom tested positive for a TTR gene variant associated with hATTR amyloidosis less than 12 hours before her bone marrow biopsy, rendering that painful test unnecessary.
I must note a couple of things so I don’t sound whiny and ungrateful: 1) Mom had been through so many tests—some invasive, a few pretty painful—so we were relieved to have a name for what ailed her, and 2) though four months of tests and questions seemed like a lot to us, her diagnosis came relatively quickly. hATTR amyloidosis often stumps folks in the medical community because its symptoms mimic so many other conditions, sometimes leaving patients suffering for years without a diagnosis.
It’s in the Genes
Our genetic counselor stressed the importance of understanding how hATTR amyloidosis can be passed down through families. Genetic counseling can help folks understand their chances of developing the condition, as well as make them familiar with the testing process and implications of a diagnosis. Genetic counselors also can help people understand the issues related to genetic testing—from personal risk to possible insurance impact— and can help determine if a genetic test may be right for them.
hATTR amyloidosis is caused by a variant or change in the TTR gene. This gene change affects the function of a protein called transthyretin (TTR). The condition is inherited in an autosomal dominant fashion, meaning a person needs to inherit only one copy of the affected gene from one parent in order to develop the disease. Everybody gets two copies of the TTR gene, one inherited from each parent. When one parent carries a variant in the TTR gene, each child will have a 50 percent chance of inheriting that variant. However, inheriting the TTR gene with a variant does not necessarily mean that he or she will develop hATTR amyloidosis.
My mom, one of six children, would need to discuss this with her siblings in the hopes they’d all get tested. She’d done the heavy lifting; they would need to have only a blood or saliva test to find out if they’d inherited the variant.
Our genetic counselor made it even easier. She supplied us with detailed information about hATTR amyloidosis and included geneticists in every city where family members reside. She also noted that a family member can inherit the TTR gene with a variant but having the variant does not mean hATTR amyloidosis is a given. Put simply: A person can carry the variant without ever developing the disease.
Still, only one of Mom’s siblings—her youngest sister—was tested (she doesn’t have the variant, so her only child, a son, doesn’t need the test). The remaining brothers and sisters have dragged their feet about testing, even though they all have young adult grandchildren on the verge of building lives and families. This information could be vital in their decision to have children—or not.
As much as I hate needles, I was tested last fall. What’s that saying? Knowing is half the battle. While I’m not showing any symptoms of hATTR amyloidosis, I did test positive for the genetic variant. The way I see it, my dark cloud is lined with a double layer of silver: I don’t have children, so this branch of the variant stops with me, and by knowing the results now, I’m better prepared should I start seeing signs of this disease down the road.
Genetic Testing 101
One option for genetic testing is through the Alnylam Act® program. Alnylam Act®, available through a healthcare professional, can be used to help confirm a diagnosis of hATTR amyloidosis. It provides no-charge, third-party genetic testing and counseling for patients 18 years and older who have a suspected diagnosis of hATTR amyloidosis or a confirmed family history of the condition. This testing can detect all possible TTR gene variants. While Alnylam provides financial support for this program, tests and services are performed by independent third parties. Healthcare professionals must confirm that patients meet certain criteria to use the program. Alnylam receives de-identified patient data from this program, but at no time does the company receive patient identifiable information. Alnylam receives contact information for healthcare professionals who use this program. Genetic testing is available in the U.S. and certain other countries, but genetic counseling is available only in the U.S. Healthcare professionals and patients who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use or support any Alnylam product. In addition, no patients, healthcare professionals, or payers, including government payers, are billed for this program.
In addition to genetic tests ordered by your doctor, direct‑to‑consumer genetic services, like 23andMe, are available for purchase to help you learn more about how genetics may influence your risk for certain hereditary conditions. In April 2019, 23andMe released a new Hereditary Amyloidosis (TTR-Related) Genetic Health Risk report, supported in part by Alnylam, that informs a person if he or she is a carrier of one of the 3 most common TTR variants in the U.S. This report does not identify all TTR variants linked to hATTR amyloidosis, nor does it diagnose hATTR amyloidosis or any other health conditions. 23andMe customers are encouraged to speak with a healthcare professional if they believe they may have hATTR amyloidosis.
For additional information and support check these resources:
- Amyloidosis Foundation: amyloidosis.org
- Amyloidosis Support Groups: amyloidosissupport.org
- Amyloidosis Research Consortium: arci.org
- The Foundation for Peripheral Neuropathy: foundationforpn.org/
- National Organization for Rare Disorders: rarediseases.org
- Global Genes: globalgenes.org
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