Hypertriglyceridaemia: Genetic Diagnosis and the Role of NGS in Lipid Disorders
This review covers the spectrum of primary hypertriglyceridaemia syndromes, from familial combined hyperlipidaemia to familial chylomicronaemia, emphasizing that standard lipid profiles are insufficient for detailed diagnosis. The authors highlight the utility of apoB100, apoE genotyping, and next-generation sequencing for characterizing patients with triglycerides above 10 mmol/L. For clinical laboratories, the article reinforces the growing need for expanded molecular and protein assays beyond routine lipid panels in specialist settings.
The original study
Hypertriglyceridaemia: an update.
- Authors
- Wierzbicki AS, Kim EJ, Esan O, Ramachandran R
- Journal
- Journal of clinical pathology
- Type
- Journal Article, Review
- PMID
- 35710321
Original abstract
Triglycerides (TGs) form part of the standard lipid profile. Elevations in TGs are associated with increased cardiovascular disease risk through triglyceride-rich lipoprotein particles found as part of non-HDL cholesterol. Many elevations of TGs are secondary to other causes, but primary hypertriglyceridaemia syndromes need to be identified. The genetic causes of hypertriglyceridaemia range from familial combined hyperlipidaemia through the autosomal recessive remnant hyperlipidaemia (related to apolipoprotein E variants) and familial chylomicronaemia syndromes. Patients with primary hypertriglyceridaemia >10 mmol/L require characterisation and specific intervention. Simple lipid profiles do not provide adequate information for detailed diagnosis and additional assays such as apolipoprotein (apo)B100, apoE genotype and next-generation sequencing may be useful. Management of raised TGs includes optimising diet, reducing exacerbating factors as well as lipid-lowering medications such as statins, fibrates, niacin and omega-3 fatty acids. Novel medications for orphan disease indications such as familial chylomicronaemia syndrome include volanesorsen, evinacumab and other antisense therapeutics. Extreme hypertriglyceridaemia syndromes, especially chylomicronaemia syndromes, which can be exposed by pregnancy or other factors are a medical emergency and require admission and specialist management sometimes including plasma exchange.