Rare inherited disease uncovered by brother's death

In ATTR-CM, the transthyretin protein is produced in an abnormal shape, and causes cardiomyopathy when it is deposited in the heart muscles. — TNS

The majority of policemen smoke to cope with stress.

Edward Palon was one of them.

The ex-cop started smoking at the age of 27, and puffing 40 sticks every day was a normal affair.

Other than smoking, the Bidayuh great-grandfather led a pretty healthy lifestyle at his home in Kampung Duras, a village roughly 30km from Kuching, Sarawak.

He cooked healthy meals daily for his family of six, had the occasional drink on special occasions, and tended to his garden where he plants fruits and vegetables.

He retired at 54, but after he touched 60, he “felt different”.

“When I worked very hard to cultivate my land, say for an hour or so, I would get chest pains, but I didn’t know I had three blocked heart arteries then.

”It was one Sunday in 2012 when I got home after church service and lunch.

“I drank some iced water and the chest pains worsened – I almost fainted.

“Immediately, I called my third daughter who lives 20 minutes away and she rushed over to take me to the hospital where I was confirmed to have suffered a heart attack,” the 77-year-old recalls on a video call.

He was referred to the Sarawak Heart Centre and had two stents inserted two weeks later.

Edward’s life returned to normal after that, although he cut down on his gardening work.

“My dad is a workaholic, he must always find things to do – he cannot sit still!” interjects his second daughter, Angela, a 52-year-old preschool teacher.

His cardiologist then sent him for six months of counselling to stop smoking.

Edward successfully quit smoking and was even awarded a certificate for his dedication and discipline.

Alas, it only lasted a few years and he picked up the stick again.

“Yes, I’m still smoking!” he admits, gazing downwards like a guilty child.

“I stopped for three years, but went back to it.

“All my friends smoke and it’s hard to be the only one not smoking.

“But I only smoke 20 sticks now,” he says defensively, laughing.

Over time, Edward noticed that his hands would sometimes go numb and he was having difficulty gripping objects – plates would slip from his fingers.

As the family chef, he continued to cook scrumptious meals and ignored the signs.

Besides, he was also the main caregiver for his wife, who is bedridden after suffering a stroke five years ago.

He had to ensure her meals were nutritious.

An unexpected inheritance

The Palon family, consisting of Edward (sitting, left), his wife (sitting, right) and their five children, including Angela (second from right), in 2018. — Photos: EDWARD PALON

In 2020, Edward’s older brother passed away from heart failure at the age of 79.

Prior to his death, he was diagnosed as having transthyretin amyloid cardiomyopathy (ATTR-CM) – a rare, underdiagnosed and potentially fatal disease of the heart muscle.

In ATTR-CM, a protein called transthyretin, which is predominantly produced in the liver and normally circulates in the bloodstream, becomes misshapen and builds up in the heart, nerves and other organs.

When these amyloid deposits build up in the heart, the walls can become stiff, making the left ventricle unable to properly relax and fill with blood – this is called cardiomyopathy.

As the condition progresses, the heart can lose its ability to squeeze hard enough to pump blood out of it, ultimately leading to heart failure.

According to Sarawak Heart Centre cardiologist Dr Oon Yen Yee, Edward’s brother was the first person in his family who had fullblown heart failure, which is typical of ATTR-CM.

“Just before he died, he informed us that his older sister had also died of heart failure and that his younger brother (Edward) also had heart problems.

“He suspected they could have ATTR-CM as well.

“Since they were also our patients, we managed to retrieve their records and images from our electronic data, and discovered that they had the same heart problem, so we knew it is likely inherited.

“We contacted Edward and advised him to go for genetic testing, and true enough, he came back positive for the hereditary mutation,” she says.

There are two types of ATTR-CM.

In hereditary ATTR-CM, which can run in families, there’s a variant in the transthyretin gene, which results in amyloid deposits in the heart, nerves, and sometimes, the kidneys and other organs.

Symptoms may start as early as age 20 or as late as 80.

The second type is wild-type ATTR-CM, in which there is no variant in the transthyretin gene and does not run in families.

It most commonly affects the heart, and can also cause carpal tunnel syndrome and pain and numbness in the hands and feet, called peripheral neuropathy.

Symptoms usually start after age 65.

Both types primarily affect males.

Slowing down progression

Awareness of ATTR-CM is low, even among healthcare professionals, and patients often have to consult multiple specialists before a diagnosis is made.

Gardening is one of Edward's greatest loves and here he is tending to one of his fruit trees.

This low understanding of the disease, coupled with significant overlap of the symptoms with other diseases, results in late diagnosis and poor outcomes.

Thankfully, Edward’s case was picked up early and he was immediately started on treatment to slow down the progression of the disease.

With ATTR-CM, healthcare professionals focus on easing the heart failure symptoms, and slowing or stopping the amyloid deposits via targeted therapies.

“Previously, a liver transplant was the only option because the abnormal protein is mainly produced in the liver and deposited in the affected organ.

“But lately, there are many emerging treatments, and now we give oral medications, which help stabilise the protein to prevent it from disintegrating and depositing into the heart muscle.

“Whatever damage is present cannot be reversed and we can only prevent further damage,” explains Dr Oon, who sees about three to four ATTR-CM cases a year.

Like many other diseases, there is no registry or epidemiological data to confirm how many cases of ATTR-CM there are in Malaysia.

In Edward’s family, the disease is being manifested at a later age, so when the symptoms start, there is already some organ damage.

“Sometimes they may be carriers, but the disease doesn’t manifest so medicines are not required, although we monitor them closely.

“Even if their disease is silent, they can still pass down the gene to the next generation, so we advise family members to get screened 10 years earlier.

“The presentation can be highly variable and some mutations are more sinister than others.

“My youngest patient is in his early 30s and his symptoms were picked up by the neurologist because his older brother also had the same problem.

“We screened him for heart involvement, and unfortunately, it was already affected,” shares Dr Oon.

Usually, screening involves taking a biopsy of the affected organ, but for the heart, doctors perform a bone scintigraphy – the same procedure used to test for bone cancer.

If it comes back positive, then a further blood test is carried out to detect another form of amyloidosis (an abnormality in certain cells).

Angela says: “My sister and I tested negative, but the doctor suggested we go for a heart check-up once in five years because so many family members have heart problems.

“My youngest brother also has a heart problem and he had a valve surgery done while he was in his late 30s, but he hasn’t gone for ATTR-CM screening yet.

“Maybe the men are afraid to go for testing!”

Supportive family

The Palons have gone through a tumultuous journey as a family, but they’re happy to share their experiences with others.

Angela (right) is one of Edward's caretakers, and also helps take care of her bedridden mother during the weekends.

Only two of Edward’s five children live nearby, two others are overseas and one has his own family to take care of.

Edward says: “It’s a disease I cannot see and feel – the only symptoms are chest pain when I do strenuous work, fatigue and the numbness.”

Angela adds: “He used to have very nice handwriting; now he seldom writes due to the numbness.

“We were initially very worried, but my dad seems to be able to handle the disease well.

“We just have to monitor him.”

Edward will soon be going for a carpal tunnel procedure to release the nerve compression in his hand.

“I make myself happy, I never worry about my health – if you worry too much, you get more and more sick!

“I don’t have any high blood pressure, but after taking all these heart medications, my blood pressure has gone up!

“Thankfully, everything else is normal,” he says.

Life goes on and every morning, Edward is up before the rooster crows – that is by 5.30am.

Then he hops on his motorbike and rides to the shop for a cup of coffee – a routine activity for him.

It’s the simple pleasures that bring him much happiness.

In a 2018 study published in the journal Neurology and Therapy, it was found that the levels of depression and anxiety that affected caregivers of ATTR-CM patients were very high and their job productivity declined significantly.

Due to the physical impact ATTR-CM has on the patient, almost half of them were unable to complete basic household chores due to limited mobility.

This resulted in caregivers spending more than 45 hours each week – some six hours of each day – giving care.

Angela, a grandmother of three, says: “My dad looks after my mum during the weekdays – he does the morning shift, and at night, my younger sister will go over to settle my mum.

“Every weekend, it’s my duty and I go back to dad’s place to give him some time off.

“That’s when he runs out to the garden to plant more veggies!

“Whenever dad needs to go for a doctor’s appointment, my sister will take him as I cannot leave my preschool kids alone.

“We try to juggle our schedules around.”

Edward’s land is thriving with all sorts of vegetables – chillies, terung asam, bitter gourd and more – all of which he uses to cook.

“He really is a good cook,” says a proud Angela, gazing lovingly at her father.

“But I hate washing!” whispers daddy dearest.