Global perspective of paediatric familial hypercholesterolaemia: analysis from the EAS FHSC registry on over 11,200 children and adolescents with heterozygous familial hypercholesterolaemia from 44 countries

Presented at EAS 2022 by Kanika I. Dharmayat (London, UK)

Introduction and methods

Familial hypercholesterolemia (FH) is a common genetic condition with a prevalence of 1 in 311 in the general population. However, less than 10% of affected individuals have been identified globally. Early identification and early intervention of FH is critical to reduce the risk of premature CVD. The Global FH Studies Collaboration (FHSC) network and registry was established in 2015 to improve global identification of FH.

The objective of the current analysis was to characterize children/adolescents with FH in the FHSC registry. These data are important to begin to inform contemporary approaches to identify children/adolescents with FH worldwide.

From the overall cohort from the FHSC registry (n=63,093), a total of 11,231 children and adolescents (<18 years) from 44 countries with probable/definite HeFH were included in this analysis.

Main results

• All regions of the world were represented in the cohort. Notably, >90% of the cases where from Europe.
• 33% of the children in the registry were an index case (i.e. first person in a family to be identified with FH). 67% were non-index cases, meaning that these children were identified through cascade screening.
• 50% were girls, median age at FH diagnosis was 9.1 years (IQR: 5.3-13.0). Physical signs of FH were rare (corneal arcus: 0.9%; xanthoma: 2.2%). 0.3% had CAD.
• 72.7% of children/adolescents were identified by a genetic test. In other cases, FH diagnosis was based on clinical criteria. Remarkably, LDL-c at diagnosis varied depending on the diagnostic criteria that were used. Children who were identified with DLCN and MEDPED had higher LDL-c levels, compared with children who were identified by a genetic test (gold standard). Using these clinical criteria could potential lead to mis-diagnosis of children with lower LDL-c levels, said Dharmayat.
• 27% of children/adolescents with FH were on lipid-lowering medications (LLM). Amongst those, 52% were initiated on LMM after the age of 10 years. Overall, 13.4% achieved the recommended LDL-c threshold of <130mg/dL.
• It was found that LDL-c is already high in the first year of live in children with FH.

Conclusion

This analysis in a large, global FH registry established that the majority of children/adolescents diagnosed with FH are non-index cases. Physical signs of FH in children were rare and LDL-c is high at all ages, even at the 5th percentile, compared with children without FH.

Dharmayat ended her presentation by saying that 1 child with FH is born every minute, and it has been estimated that there are 6.4 million children (0-14 years) with FH globally. Dharmayat concluded that screening in childhood with a LDL-c measurement and/or genetic testing is needed to correctly identify children with FH in order to prevent early manifestation of ASCVD.

– Our coverage of EAS 2022 is based on the information provided during the congress –