ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 12.12 | DOI: 10.1530/ey.19.12.12

ESPEYB19 12. Type 2 Diabetes, Metabolic Syndrome and Lipids Hyperlipidemia (6 abstracts)

12.12. Childhood hypertriglyceridemia: is it time for a new approach?

Sunil B & Ashraf AP

Current atherosclerosis reports 2022;24(4):265-75. doi: 10.1007/s11883-022-01000-2

Brief Summary: This review article discusses emerging therapies targeted at specific genes, proteins and enzymes to selectively alter triglyceride (TG) metabolism.

Comment: Hypertriglyceridemia is a long-neglected major cardiovascular disease (CVD) risk factor. Recent epidemiological data show that both moderate and severe hypertriglyceridemia are associated with substantially increased cardiovascular disease risk and long-term mortality. This is specifically significant for hypertriglyceridemia beginning in childhood. About 10% of children have circulating TG >150 mg/dl.

Concentrations of fasting TGs are stratified into: normal <130 mg/dl, high ≥130–499 mg/dl, very high ≥500–999 mg/dl, severe 1000–1999 mg/dl and very severe ≥2000 mg/dl. Borderline high TGs are mostly due to acquired factors, such as high carbohydrate intake, obesity, physical inactivity, cigarette smoking, excess alcohol intake and oral hormonal contraception. High values of TGs generally result from a combination of acquired and genetic factors. Very high TGs are typically due to genetic defects. Severe elevation of TG poses a risk of acute pancreatitis, while mild-to-moderate hypertriglyceridemia increases the risk for premature atherosclerotic CVD, and has increasingly been linked with NAFLD.

Indications for genetic testing, dietary recommendations and pharmacotherapy management are detailed in the review. An excellent summary is presented of new drugs that were developed over the last two decades, including their mechanisms, their effect on lowering TG levels, side effects, ongoing clinical trials in children and FDA/EU approval, as relevant. The new agents include drugs that (1) reduce apolipoprotein C3 [antisense oligonucleotides – volanesorsen and AKCEA-APO-CIII-LRx] and small interfering RNA (siRNA) molecules-AROAPOC3, (2) target ANGPTL3 [ANGPTL3 monoclonal antibody (evinacumab) and GalNac-conjugated antisense oligonucleotide that target ANGPTL3 mRNA in the liver, such as vupanorsen/IONIS-ANGPTL3-LRx] and siRNA AROANG3, or (3) inhibit microsomal TG transfer protein-lomitapide.

In addition to this review, a “Grand Rounds” article in the Journal of Pediatrics1 describes the clinical presentation, evaluation and management of a 15-year-old male with TG levels >2000 mg/dl.

Reference: 1. Wilson DP, Williams L, Kavey RW. Hypertriglyceridemia in Youth. The Journal of Pediatrics 2022;243:200–07. doi: 10.1016/j.jpeds.2021.12.017 [published Online First: 2021/12/21].

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