Family hypercholesterolemia due to LDLR gene in Vietnamese children: characteristics of phenotype and genotype

Background

Familial hypercholesterolemia (FH) results in elevated LDL cholesterol, contributing to atherosclerosis and early-onset cardiovascular disease. Mutations in the low-density lipoprotein receptor gene are the most common cause of familial hypercholesterolemia. Information regarding hypercholesterolemia in low- and middle-income nations is inadequate. This research aimed to characterise the phenotype and genotype of Vietnamese children diagnosed with familial hypercholesterolemia.

Methods

This study included twenty-one children diagnosed with familial hypercholesterolemia from 15 unrelated families. Data regarding physical characteristics, biochemical testing, cardiac ultrasound, coronary angiography, and dual-source computed tomography were gathered at diagnosis and follow-up. Next-generation and Sanger sequencing were performed to identify disease-causing variants in twenty-one index cases.

Results

We found eighteen heterozygous and two homozygous/one compound heterozygous FH cases. Fourteen distinct variants were identified, with the most prevalent being c.664 T > C and c.681C>G, and exon 15 deletion. Furthermore, we identified the c.161A>C variant, which remains unreported in the literature. The median age at diagnosis was 6.7 years (0.5–17.5) and 8.3 years (6.3–13.3) in heterozygous and homozygous/compound heterozygous groups, respectively. 100 % homozygous/compound heterozygous cases and 16.7 % heterozygous cases presented xanthomas. The median plasma levels of LDL in heterozygous and homozygous/compound heterozygous groups were 6.6 mmol/l (3.8–12) and 10.8 mmol/l (10.7–11.7), respectively.

Conclusions

FH can appear early in childhood, and xanthomas primarily manifest in homozygous FH patients. LDLR gene variants in Vietnamese FH children were diverse, with 14 variants in 21 cases.