SINGAPORE – A child here was just 2½ years old when he was started on cholesterol-lowering medication. At that time, the toddler had an extremely high level of LDL (low-density lipoprotein), the bad cholesterol – it was 15 millimoles per litre (mmol/L) compared with the normal level for a toddler of below 3.4 mmol/L.

He is one of about 50,000 people here – or one in 140 – who are at very high risk of getting a premature heart attack, below the age of 50 years for men and 60 years for women, unless they receive treatment early. In Singapore, the median age of getting a first heart attack is 70.

The very high risk group have a condition known as familial hypercholesterolemia (FH), caused by an inherited gene mutation, which could mean having very high LDL levels from birth.

If their LDL is not controlled, their risk of getting a heart attack is 22 times that of a healthy person without the mutation.

In 2020, 931 people here under the age of 50 had heart attacks, out of whom 15 were under 30 years old.

Associate Professor Tavintharan Subramaniam, an endocrinologist at Khoo Teck Puat Hospital (KTPH), strongly believes that identifying those with FH and intervening early would result in fewer heart attacks here and better quality of life for those affected.

He started a programme in 2015 to screen young people with heart problems for the gene mutation that causes FH. It is called cascade screening, because every time someone with the mutation is identified, the screening is extended to their family members.

As the gene mutation is inherited, there is a high chance a person with FH has close relatives with the same condition.

Those diagnosed with FH are started on intensive cholesterol-lowering medication such as statins.

Cascade screening is free as funding was provided by Alexandra Health.

In 2022, the team was given a larger grant by Precision Health Research Singapore, set up by the Government to promote data-driven healthcare. This allowed the team to accelerate the process.

To date, it has screened over 1,000 patients and about 40 per cent have the gene mutation.

Professor Tan Chorh Chuan, Singapore’s chief health scientist, said people with the mutation need to be picked up early before they have a heart attack in their 20s, 30s or 40s.

“You’ll have a whole bunch of people who are taking statins, but then they don’t have a heart attack early, they don’t need to go to hospital,” he said, explaining why early identification could prove cost-effective.

Prof Tan added that Prof Tavintharan’s pilot programme is to get data to show if there is real benefit.

Only about 40 per cent of the index cases – the first person in a family diagnosed – clinically diagnosed with FH were actually found to have a gene mutation after the screening. The rest have other causes for their high cholesterol levels. Treatment for both groups is the same.

The United States Centres for Disease Control and Prevention says early intervention reduces the risk of coronary artery disease by 80 per cent.

Symptoms of FH include bumps or lumps at joints, swollen or painful Achilles tendon, and yellowish areas around the eyes.

Doctors say one of the earliest known cases of FH could be the woman who posed for Leonardo da Vinci’s famous painting, the Mona Lisa. She died aged 37. The small yellow lesion above her left eye and the bump on her right hand depicted in the painting are symptoms of FH, doctors say.

An article published in Current Cardiology Reviews in 2008 said: “This portrait painted in 1506 is probably the first evidence of familial hypercholesterolemia.”

Prof Tan said FH screening has become possible only in recent years with easily available gene sequencing.

FH is caused by a defect at chromosome 19. People have 23 pairs of chromosomes, with half of each pair coming from one parent.

Chromosome 19 creates the receptors to channel cholesterol from the blood to the liver where it is cleared. If one gene out of four pairs (or one out of eight genes) at chromosome 19 is defective, it is less able to help the body clear itself of the cholesterol, which then accumulates in the blood. With one defective gene, effectiveness of that pair is down by 50 per cent.

Elevated cholesterol levels contribute to the formation of plaque in arteries, causing them to narrow, which could lead to a heart attack if blood flow to the heart muscle is reduced or cut off.

It is rare for a person to have two defective, cholesterol-linked genes, which makes the problem a lot more serious. Prof Tavintharan said that out of 1,162 index patients screened, 23 had more than one defective gene, but from different pairs.

Another three had both genes in one pair that were defective – this means both parents also have FH. Almost all the children of someone with more than one defective gene will have FH.

Unfortunately, about half of those identified with the mutation here have declined to have their family members tested. The reasons include not wanting to worry them or their family members not having the time to do the screening.

From the other half, two family members on average would get tested. Out of a total of 460 family members tested, 180 have the gene mutation.

Some of these 180 people were already being treated for high cholesterol levels. But because they have FH, their treatment needs to be more aggressive, so the KTPH team would provide them with a letter to their doctor explaining what needs to be done.

Prof Tavintharan said there is ongoing research to see if there are other genes or a multiple of genes with smaller LDL impact that cumulatively could cause FH.

Due to greater awareness of FH here in recent years, more children with the condition are being picked up.

Professor Fabian Yap, head of paediatric endocrinology at KK Women’s and Children’s Hospital (KKH), said the hospital used to diagnose “up to five children with FH a year”. Since 2020, it has been seeing up to 10 such cases a year.

Prof Yap said younger children tend to have yellowish streaks, patches or lumps on the skin surface. Older children may have thickened Achilles tendons, due to fatty deposits.

“KKH will be launching a new clinic next year to cater to the increasing number of children diagnosed with FH. We anticipate that in the coming years, more children will be identified with FH mainly due to increasing awareness of the importance of lowering cholesterol levels from childhood,” he added.