Most children with overgrowth are diagnosed by successive screening, albeit too late and ineffective

The researchers urge the development of a global screening strategy that would identify the more than 6 million children with family overgrowth.

An analysis has shown that children with familial hypercholesterolemia (FH) are frequently diagnosed later, often through back-to-back screening, and have elevated levels of LDL cholesterol compared to children without the genetic disorder.

The findings, presented this week at the European Atherosclerosis Society (EAS) 2022 conference, underscore the importance of an effective, internationally adaptable screening strategy, especially since some countries do not have access to advanced genetic testing, the researchers say.

“One child is born with hyper-hip-hopper every minute,” Kanika Darmayat, MPH (Imperial College London, England), said during a recent clinical trial session. If we want to do the screening in childhood, we use either low-density lipoprotein cholesterol [concentrations] Or genetic testing, we can correctly identify the 6.4 million children who have family overgrowth now so that we can help them and prevent any manifestations of [atherosclerotic cardiovascular disease]. ”

FH is an autosomal dominant genetic disease caused by mutations in the genes that encode LDL receptors (LDLR), apolipoprotein B (APOB), or a protein proprotein converter subtilisin/kexin type 9 (PCSK9). The global prevalence of FH is approximately one in 300 people of all ages, which means that there are approximately 25 million people worldwide with the genetic disorder, including more than six million children.

“Despite being a common condition globally, less than 10% [of cases] Dharmaiat said. “Individuals with FH have elevated LDL-cholesterol levels from birth, so it becomes essential to recognize them early so that we can intervene and treat early and change the prognosis of individuals with FH to match the expectations of the general population.”

The median age of diagnosis of hypercholesterolemia among adults in the Familial Hypercholesterolemia Collaboration (FHSC) was 44.4 years, with only 2.0% of adults in the registry diagnosed during childhood. This late diagnosis represents a missed opportunity for treatment and an increased risk of atherosclerotic cardiovascular disease (ASCVD) – approximately one in six adults has been diagnosed with coronary artery disease.

It was identified by successive screening

For the new study, the researchers, including Principal Investigator Kausik Ray, MBChB, MD (Imperial College London), sought to shed light on the characteristics of children/adolescents with FH in FHSC, including the ages at which they were determined, and how they were determined. and how they were managed.

Of the total group of 63,063 patients with FH, 11,231 were children/adolescents with a probable or confirmed diagnosis. More than 92% of cases were from Europe, with only 3.8% from North, Central and South America. 1.2% of cases are from Africa; 1.1% of Eastern Mediterranean countries; and 1.8% from Southeast Asia and the Western Pacific. A third of the diagnosed cases were index cases, meaning the child was the first person in the family to be diagnosed with FH. The remaining unindicated cases were diagnoses that occurred through successive screening after a parent and/or close relative had an ASCVD event.

On average, children were 9 years old at the time of diagnosis. Physical signs of FH, such as corneal arch or xanthomas, were extremely rare and approximately three-quarters of them were identified through genetic testing. Of those in FHSC, 27% were on lipid-lowering medication and more than half of these patients had started LDL-lowering therapy after age 10.

When the treatment was started, there was a decrease in LDL cholesterol levels. “However, these children are still far from reaching the EAS recommended minimum of 130 mg/dL,” Darmaiat said.

By the age of 12 months, she added, babies with FH had significantly increased LDL levels compared to their counterparts without FH. For those with LDL levels in the 5th percentile, LDL was still significantly higher when compared to children without FH.

Recognizing children or teens with hyperhydration can present challenges. Genetic testing is the gold standard, but it is not available everywhere. Also, some of the criteria used to diagnose FH, such as the Dutch Lipid Clinic Network (DCLN) and the MEDPED criteria, were not adapted for children or adolescents, although Simon Broome’s criteria were modified. Children’s lipid concentrations vary by age and gender, Darmaiat said, which could lead to misdiagnosis.

The researchers note that sequential screening is not an effective method for catching children and/or adolescents with FH, and suggest that a systematic screening for elevated levels of LDL cholesterol at birth or even during vaccination in the child’s first year of life be undertaken in areas where genetic testing is not available. “If we measure low-density lipoprotein cholesterol in childhood, we can get a good understanding of the people affected by FH, since levels of low-density lipoprotein cholesterol are much lower than in children who do not have overgrowth,” He said Dharmatians.

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