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Familial Hypercholesterolemia in Children and Adolescents
Quick Takes
- Genetic diagnosis was more common in children and adolescents from high-income countries than in children and adolescents from non–high-income countries.
- Lipid-lowering therapy remains underutilized in children and adolescents with HeFH.
- Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection of HeFH in children and adolescents.
Study Questions:
What are the characteristics of children and adolescents with heterozygous familial hypercholesterolemia (HeFH) that may assist in the identification and management of familial hypercholesterolemia (FH)?
Methods:
A cross-sectional study design was used to examine data from children and adolescents <18 years old with a clinical or genetic diagnosis of HeFH at the time of entry into the FHSC (Familial Hypercholesterolemia Studies Collaboration) registry between October 1, 2015, and January 31, 2021. Registry data were collected from 55 regional or national registries in 48 countries. Data from participants who self-reported a history of FH and suspected secondary hypercholesterolemia were excluded from this study, as were those with an untreated low-density lipoprotein cholesterol (LDL-C) of ≥13.0 mmol/L. The primary outcomes were current identification and management of children and adolescents with FH.
Results:
A total of 11,848 of the 63,093 individuals in the FHSC registry were children or adolescents <18 years old with HeFH. Of the 11,843 children/adolescents, 5,756 (50.2%) were female, 5,720 (49.8%) were male, and 372 individuals' data was missing information on sex. Median age at registry entry was 9.6 years (interquartile range [IQR], 5.8–13.2). A total of 10,099 (89.9%) had a final genetically confirmed diagnosis of FH, and 1,136 (10.1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5.2%) individuals. Genetic diagnosis was more common in children and adolescents from high-income countries than in non–high-income countries. FH-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon but were more common in non–high-income countries. 7,557 of included children or adolescents were not taking lipid-lowering medication and had a median LDL-C of 5.00 mmol/L (IQR, 4.05–6.08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliance on more extreme phenotypes could result in 50-75% of children and adolescents with FH not being identified.
Conclusions:
The authors concluded that clinical characteristics observed in adults with FH are uncommon in children and adolescents with FH. Hence, detection in this age group relies on the measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination lipid-lowering medications to reach recommended LDL-C targets early in life.
Perspective:
This study provides compelling data that support efforts to improve identifying HeFH early in life. Further research is warranted to determine if increased genetic testing and/or LDL measurement is effective on a population level. Outcomes should include initiating lipid-lowering therapy, particularly given the low rates observed in these registry data.
Clinical Topics: Dyslipidemia, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Primary Hyperlipidemia, Prevention
Keywords: Hypercholesterolemia, Hyperlipoproteinemia Type III
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