Dan and Diana Matheson have both been diagnosed with hereditary amyloidosis (ATTRv) in the last four years. While Dan’s diagnosis took five years, Diana’s only took two, and that difference has had a profound effect on their current health and quality of life. Here, they reflect on their paths to diagnosis and treatment. They also explain how family letters from a century ago reveal how their own experiences may be just the “tip of the iceberg”

Dan’s journey from his early symptoms of hereditary amyloidosis (ATTRv, also known as hATTR) to his diagnosis took five years. His first symptom of the disease was carpal tunnel syndrome, which started in both his wrists in 2014. Neither he nor his doctors realised that the underlying cause was ATTRv. “But even if they had diagnosed it back then, it wouldn’t have mattered, because back then there was no treatment,” Dan says.

With hindsight, the other symptom at that time was fatigue. Dan used to do “a fair amount of running” but gave it up: “I couldn’t keep up with the guys because I’d get out of breath. I just chalked it up to just being older and out of shape, having no time, and running my business.”

In September 2016, Dan noticed how hard it had become for him to do anything physical. One day, he noticed how pushing his wife’s wheelchair on a gravel path had left him “sweating like a racehorse”.

He went to see his doctor, who referred him to a cardiologist, who referred him to a haematologist. But his amyloidosis went undiagnosed.

In 2018, Dan began to receive private medical care, and when his new doctor questioned him about his family’s health history, Dan sought Diana’s input. When she reported that their mother had been diagnosed with amyloidosis of unknown origin, Dan was referred for genetic testing to see if he had the hereditary form of amyloidosis.

Within weeks he had a diagnosis: “They informed me, ‘You have hereditary amyloidosis, and you have three to five years to live.’ That’s a lot of information to handle—it was a day that my wife and I won’t forget.”

In 2019, Dan’s doctor prescribed him a recently approved drug, but unfortunately by then—three years after his first symptoms started—Dan already had permanent nerve damage and congestive heart failure (when the heart can’t properly pump blood around the body).

In 2018, Dan had a brain haemorrhage and spent a week in intensive care at hospital, and in 2022, he blacked out behind the wheel of his car and crashed into a tree—he could “very easily” have been killed, he says. Both events were because of the problems amyloidosis has caused for his heart.

“All my life I’ve been in shape; I have no heart disease at all, yet I have to be on a blood thinner to protect me from having a stroke… the blood thinner is a big pain because I’m always cutting and bruising myself”. He requires other medication too: “a drug to slow my heart rate to allow it to compensate for being thick and stiff, and a lot of diuretics to reduce the swelling (oedema) throughout my body”. Dan has also had an implantable cardioverter defibrillator (ICD) implanted. (An ICD delivers an electrical shock to the heart if it starts beating in a potentially dangerous way.)

Dan’s active lifestyle has changed radically in the last few years, with his physical and even mental faculties affected by the disease. Diana explains how she has seen him go “from being a fit runner and very athletic and going on amazing motorcycle tours for weeks with his buddies to struggling up and down stairs, to having to watch everything he eats, and changing how he lives.”

Dan explains: “Amyloidosis has totally impacted on my quality of life. I’ve lost 20 pounds of muscle and I’ve lost a massive amount of appetite. It’s affected my interaction with friends and my ability to exercise or walk my dogs… doing my housework, tying up my shoes, choosing what I wear.”

“It impacts absolutely everything in my life—other than my sense of humour.”

– Dan

Diana’s earliest symptoms of amyloidosis were in the summer of 2019. “I always felt like I was going to get the flu. But by noon, I’d start to get more energy. That, along with, unfortunately, constipation, which would kind of linger.”

Then, in 2020, Diana’s feet became painful, which she put down to pushing too hard when she was running. But over the next few months, this pain seemed to spread to her knees as well.

Dan, mindful of his own diagnosis, pushed Diana to have her heart checked for signs of amyloidosis. So she went for an echocardiogram, which showed it to be “absolutely perfect”.

But in 2021, Diana’s feet started to hurt a little bit more. She also had problems with her hands, and that particularly worried her because she is a pianist. “I was noticing a bit of numbness, a little stinging (just like bee stings), and just feeling I wasn’t making accurate landings on my keys,” she explains.

A neurologist she consulted told her that she was fine and just had “a little low-grade polyneuropathy (nerve damage)” in her feet and nothing wrong with her hands.

Dan was more concerned than Diana was herself and insisted that she have a genetic test for ATTRv, which she arranged in late August. “I was very nonchalant about it,” she says.

When the results came in October 2021, eight weeks later, Diana was shocked to see that she had the same genetic variant as Dan. She really didn’t think she would because her symptoms seemed so different to her brother’s.

“I was completely devastated. I saw my mother die from this, but I’ve also watched my brother deteriorate and suffer, and that’s been heart-breaking,” she says. Her fear was that she would have only a few years left to live and that she would be unwell for much of that time.

Dan introduced her to his cardiologist who “jumped on the phone with me at nine o’clock on a Friday night the week I was diagnosed. He basically said, ‘You’re going to be fine.’” He reassured her that her prognosis was good because of her early diagnosis.

Soon afterwards—just eight weeks after the genetic test results—Diana had her first treatment, and her symptoms have not noticeably progressed since then.

She is maintaining an “active and healthy lifestyle”; she goes running and she goes to the gym three or four times a week. Her fingers feel “great”, and she is continuing to teach piano.

After their diagnoses, Dan and Diana looked back at letters written in the 1920s by their great grandmother, Miriam Anne, who was then in her mid-50s, to their grandmother, Edna. Dan and Diana wanted to work out if there was a family history of amyloidosis even before their mother’s diagnosis.

“The lines in the letters that really hit home for me,” Diana explains, “was when my great grandmother talked about her chronic fatigue… She would feel pleased if she got out for a walk, or if she was able to have a family dinner—her lifestyle had become very difficult.” She also referred to other symptoms like constipation, indigestion, foot pain and a lack of energy. What she described closely matched Diana’s symptoms. “My symptoms were her symptoms,” she says.

Looking back to their mother’s poor health in the late 1990s, Diana was able to “connect the dots” more: her mother’s chronic fatigue then reminds her very much of Dan’s symptoms now, she says.

“In the summer of 1998 (six years before she died), Mom was in Scotland and had no energy to even just walk up a hill. Dad even had to carry her purse.” Sadly, Dan and Diana’s mother died in 2004 because of congestive heart failure and stroke caused by the amyloidosis. 

“She was so brave. What I’ve gone through is nothing.”

– Dan

The letters and anecdotal evidence suggest a history of hereditary amyloidosis in Dan and Diana’s family that stretches back at least a hundred years. They believe that ATTRv may have affected not only their mother, but also their grandmother and their great grandmother—they wonder how that history will affect their nieces’ and nephews’ futures.

Fortunately, the medical advances that have been made in recent years—and that continue to be made—are improving outcomes for people who are diagnosed today.

Dan remarks on his good fortune “to have been diagnosed with the disease and to be told I have three to five years to live—but then, about a year and a half later, I’m told there is a therapy to modify the disease is truly a miracle”.

Diana has been able to access that treatment promptly thanks to her early diagnosis, and she is hugely grateful for that: ‘It was really powerful to have that care so quickly… I can’t imagine not having had that, because every day is important.”

“Doctors need training to look for the signs and symptoms of this disease as early as possible,” Dan says. “It makes such a difference—a year and a half of progress with this disease is life-altering.

“If a guy like me goes to the doctor and is diagnosed with heart issues, polyneuropathy, diarrhoea/constipation or carpal tunnel syndrome, to name a few of the symptoms, a lot of doctors, unfortunately, will not dig deeper. They simply treat those symptoms and not the underlying cause. They must start doing that.”

Diana agrees: “The family doctor is everybody’s first stop. People say, ‘I have indigestion, I’m constipated, I’m tired, my feet are bothering me’ and all of those can be easily dismissed. Who’s going to connect those dots?

“My dream would be for greater awareness at medical school level of what all these vague symptoms could boil down to. There must be so many people walking around with this. We’re just like the tip of the iceberg.

“I remember our mom telling us that she lost seven family members within a year and a half, all within their late 50s to mid-60s, and all on her side… so it’s also for people to think about why everybody is dying around the same age.

Diana concludes: “I’ve been so lucky. My brother truly saved my life by pushing me to get diagnosed. Without Dan I’d probably still be thinking I had constipation and neuropathy…”

“What’s emotionally hard for me is that my brother didn’t get the same chance.”

– Diana

References

[1] Pacemaker implantation [Internet]. nhs.uk. 2017 [cited 2023 Feb 16]. Available from: https://www.nhs.uk/conditions/pacemaker-implantation/

[2]  Morie A. Gertz MD. Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges. 2017 Jun 13 [cited 2023 Feb 16];23. Available from: https://www.ajmc.com/view/hereditary-attr-amyloidosis-burden-of-illness-and-diagnostic-challenges-article

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This digital spotlight has been made possible with financial support from Alnylam Pharmaceuticals. Interviews and writing included in these articles have been independently conducted by RARE Revolution Magazine. All opinions are those of the contributors. RARE Revolution Magazine retains all copyright. RARE Revolution Magazine and Alnylam Pharmaceuticals are not responsible for the content of external sites linked to within this article.

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