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case_report·pediatrics, gastroenterology, pediatric ophthalmology, clinical trial, systematic review·PMC10293746

Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review

Frontiers in Medicine · 11 authors, 4 centres

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TL;DR

This case report describes a pediatric patient with a novel heterozygous APOB gene variant causing familial hypobetalipoproteinemia (FHBL), who presented with fatty liver and low cholesterol. Treatment included dietary fat restriction and fat-soluble vitamin supplementation.

Full summary

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The study presents a case report and systematic literature review of heterozygous familial hypobetalipoproteinemia (FHBL). The methods involved genetic analysis of a pediatric patient and family using next-generation sequencing, and a systematic review of 19 articles covering 35 cases. The central result was the identification of a novel pathogenic frameshift variant in the APOB gene (c.6624dup[=]) causing a truncated protein, associated with the patient's hypocholesterolemia and non-alcoholic fatty liver disease. Management included dietary fat limitation and supplementation with vitamins E, A, K, D, and calcium carbonate. Limitations include that the patient also had Stickler syndrome, making it impossible to attribute all symptoms solely to the APOB variant, and the findings are from a single case and literature review.

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case_report

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pediatrics

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ORIGINAL PAPER

PMC10293746

Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review

Frontiers in Medicine

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ABSTRACT

Background Familial hypobetalipoproteinemia (FHBL) is an autosomal semi-dominant disorder usually caused by variants in the APOB gene that frequently interferes with protein length. Clinical manifestations include malabsorption, non-alcoholic fatty liver disease, low levels of lipid-soluble vitamins, and neurological, endocrine, and hematological dysfunction. Methods Genomic DNA was isolated from the blood samples of the pediatric patient with hypocholesterolemia and his parents and brother. Next-generation sequencing (NGS) was performed, and an expanded dyslipidemia panel was employed for genetic analysis. In addition, a systematic review of the literature on FHBL heterozygous patients was performed. Case report Genetic investigation revealed the presence of a heterozygous variant in the APOB ( NM_000384.3 ) gene c.6624dup[=], which changes the open reading frame and leads to early termination of translation into the p.Leu2209IlefsTer5 protein ( NP_000375.3 ). The identified variant was not previously reported. Familial segregation analysis confirmed the variant in the mother of the subject, who also has a low level of low-density lipoprotein and non-alcoholic fatty liver disease. We have introduced therapy that includes limiting fats in the diet and adding lipid-soluble vitamins E, A, K, and D and calcium carbonate. We reported 35 individuals with APOB gene variations linked to FHBL in the systematic review. Conclusion We have identified a novel pathogenic variant in the APOB gene causing FHBL in pediatric patients with hypocholesterolemia and fatty liver disease. This case illustrates the importance of genetic testing for dyslipidemias in patients with significant decreases in plasma cholesterol as we can avoid damaging neurological and ophthalmological effects by sufficient vitamin supplementation and regular follow-ups.

CITATION EXPORT

Neza Molk, Mojca Bitenc, Darja Urlep et al.. Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review. Frontiers in Medicine. (2023). https://doi.org/10.3389/fmed.2023.1106441

AUTHORS

11 · 4 CENTRES

Neza Molk, Mojca Bitenc, Darja Urlep, Mojca Zerjav Tansek, Sara Bertok, Katarina Trebusak Podkrajsek, Ursa Sustar, Jernej Kovac, Tadej Battelino, Marusa Debeljak, Urh Groselj

1Department of Pediatric Endocrinology, Diabetes and Metabolism, University Medical Center-University Children's Hospital, Ljubljana, Slovenia
2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, University Medical Center, Ljubljana, Slovenia
4Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Center Ljubljana, Ljubljana, Slovenia