A routine blood test from one year of age could identify up to 95% of affected children, allowing for early intervention and improved health outcomes.
LDL cholesterol (LDL-C) levels strongly correlate with familial hypercholesterolaemia (FH) in children aged one to 12, Norwegian researchers have found.
And using the 95th or 85th percentile of LDL-C levels as the cut-off would identify more than 88% and 94% of FH cases, respectively.
Data were obtained from Norway’s national family cascade screening program for familial hypercholesterolaemia (FH) in children, covering 1998 to 2023.
Cholesterol levels were compared between variant-positive and variant-negative children, using samples from umbilical cord blood in newborns (113) and venous blood in children aged on to 12 years (1346).
It was an unselected group of children who had one parent with a confirmed FH variant in LDLR, APOB or PCSK9.
Researchers determined the potential efficacy of cholesterol screening by comparing variant positive children with variant negative children, who were representative of the normal population.
LDL-C was significantly higher in variant positive children than variant negative children in all age cohorts from one to 12 years.
Researchers explained that although the hallmark of FH was generally hypercholesterolaemia, some children with FH presented with normal cholesterol levels at one time point, meaning one-off lipid-screening approaches could miss them.
Cholesterol-based screening approaches for FH would only be feasible from one year of age onward, they found.
While LDL-C was higher in FH newborns (1.22 mmol/L) than non-FH newborns (0.68 mmol/L) and did reach statistical significance, the overlap was large.
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Using the 95th percentile cut-off would detect less than 60% of newborns with FH, and a quarter of affected babies would be missed if using the 85th percentile.
Total cholesterol levels were significantly higher in FH compared with non-FH newborns, but still low in both groups (2.45 vs 1.93 mmol/L). There was no difference between the groups in HDL-C or triglycerides.
Calculated LDL-C in newborns was significantly higher than direct measured LDL-C but calculated and measured were similar in children aged one to 12.
Mean age at testing was seven years and around half the cohort were male. Nearly 50% of the children were heterozygous, carrying one copy of the familial variant.
The study was the first to show the true LDL-C overlap in FH and non-FH children, the researchers reported.
FH is the most common autosomal dominant cause of premature cardiovascular disease (CVD) and can accelerate the development of atherosclerosis from an early age.
Early signs of atherosclerosis were evident in the first eight years of life and more than 90% with it went on to develop CVD in adulthood, the authors wrote.
Initiating cholesterol-lowering treatment in childhood is well documented and can reduce cardiovascular risks.
Due to the cost and capacity of genetic testing, researchers concluded that screening initiatives should be based on initial cholesterol measurements.
Subsequent genetic testing would be suggested for children with LDL-C in the top percentiles, the researchers said.
Around one in 250 people have FH and it is estimated that only 10% of Australians with FH are diagnosed.
