Prevalence, genetic variants, and clinical implications of hypocholesterolemia in children

Grošelj, Urh (author), Kafol, Jan (author), Molk, Neža (author), Sedej, Katarina (author), Mlinarič, Matej (author), Šikonja, Jaka (author), Šuštar, Urša (author), Čugalj Kern, Barbara (author), Kovač, Jernej (author), Battelino, Tadej (author), Debeljak, Maruša (author)

Background and aims: In contrast to extensively studied hypercholesterolemia, knowledge of hypocholesterolemia is limited. This study aims to assess the prevalence, clinical characteristics, and genetics of children and adolescents with hypocholesterolemia. Methods: This national prospective cross-sectional cohort study was part of Slovenia's universal opt-out cholesterol screening program. The first part assessed hypocholesterolemia prevalence among 3538 children aged 5 years, randomly selected at the mandatory check-up. The second part included analysis of demographic and clinical data and genetic testing of 71 individuals with suspected hypocholesterolemia (total cholesterol [TC] < 3.0 mmol/L [116.0 mg/dL]) referred to the Lipid Clinic of University Children's Hospital Ljubljana. Results: The prevalence of hypocholesterolemia among 3538 children was 2.66 % (95 % CI: 2.13-3.19 %). Among the 71 genetically tested individuals with suspected hypocholesterolemia, those with pathogenic variants had lower TC (2.58 ± 0.44 mmol/L vs. 2.85 ± 0.42 mmol/L [99.77 ± 17.02 mg/dL vs. 110.20 ± 16.24 mg/dL]; p = 0.037) and low-density lipoprotein cholesterol (1.00 ± 0.40 mmol/L vs. 1.33 ± 0.40 mmol/L [38.67 ± 15.47 mg/dL vs. 51.43 ± 15.47 mg/dL]; p = 0.014) compared to those without such variants. Genetic testing identified pathogenic alterations in 15 subjects, including 4 novel loss-of-function variants in the APOB gene. All but one subject were asymptomatic. Conclusions: This study provides new clinical and genetic insights into hypocholesterolemia. Asymptomatic patients with hypocholesterolemia may not require further evaluation, but additional research is needed to understand hypocholesterolemia better.

• Language: English
• Keywords: APOB, children, hypocholesterolemia, next-generation sequencing, prevalence
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 6 str.
• Numbering: Vol. 400, art. 119065
• PID: 20.500.12556/RUL-167726
• UDC: 616.4-053.2
• ISSN on article: 1879-1484
• DOI: 10.1016/j.atherosclerosis.2024.119065
• COBISS.SI-ID: 228354563
• Publication date in RUL: 10.03.2025

Record is a part of a journal

• Title: Atherosclerosis
• Shortened title: Atherosclerosis
• Publisher: Elsevier
• ISSN: 1879-1484
• COBISS.SI-ID: 6621247

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: otroci, hipoholesterolemija, sekvenciranje naslednje generacije, prevalenca