ESPE Abstracts

Background and objectives: Dyslipidemia especially hypercholesterolemia attracts much more attention recently. Given different management and treatment of multiple categories, precise diagnosis becomes increasingly important. However, studies in pediatric patients lacks around the world, especially in China. Consequently, this study was designed to confirm the molecular defect of persistent hypercholesterolemia with next-generation sequencing basing on a single-center cohort of pediatric patients.

Method: Patients were collected according to including and excluded criteria. Clinical information was collected, and then, physical and laboratory examination was performed. Genetic sequencing was performed on these patients.

Results: 35 patients were included and 32 patients of them (aged 1.0-13.8 years) were finally performed with genetic sequencing. Positive results were obtained in 65% of the patients including variants of LDLR, LIPC, JAG1, ABCG5, ABCG8, LPl, et al. Of them, eight were novel. Furthermore, LDLR was the most common gene identified in these patients and ABCG5/8 ranks second. Also, 10% of the patients were identified variants from two different genes. Through analyzing patients with positive genetic results, we found that the average age was elder, and the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) were higher in patients with positive genetic results. Also, comparing with the patients with tendon xanthomas, the patients without tendon xanthomas were elder and the levels of apolipoprotein were higher. Interestingly, the levels of TC and LDL-C showed no difference in these two groups.

Conclusion: We identified 28 variants in 32 pediatric patients with persistent hypercholesterolemia, enriching genetic and phenotypic spectrum. Levels of apoB is probably a biomarker or potential therapeutic target of monogenic hypercholesterolemia. Heterozygotes ABCG5/8 variants could be underestimated in pediatric patients with hypercholesterolemia.