Incidental finding of severe hypertriglyceridemia in children. Role of multiple rare variants in genes affecting plasma triglyceride

Paola Sabrina Buonuomo, Claudio Rabacchi, Marina Macchiaiolo, Chiara Trenti, Tommaso Fasano, Patrizia Tarugi, Andrea Bartuli, Stefano Bertolini, Sebastiano Calandra

Research output: Contribution to journalArticlepeer-review


Background: The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as in other proteins, such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface) and LMF1 (a factor required for intracellular formation of active LPL). Objective: Molecular characterization of 5 subjects in whom HyperTG was an incidental finding during infancy/childhood. Methods: We performed the parallel sequencing of 20 plasma TG-related genes. Results: Three children with severe HyperTG were found to be compound heterozygous for rare pathogenic LPL variants (2 nonsense, 3 missense, and 1 splicing variant). Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG. The fifth patient with a less severe HyperTG was found to be heterozygous for a frameshift variant in LIPC resulting in a truncated Hepatic Lipase. In addition, 1 of the patients with LPL deficiency and the patient with APOA-V deficiency were also heterozygous carriers of a pathogenic variant in LIPC and LPL gene, respectively, whereas the patient with LIPC variant was also a carrier of a rare APOB missense variant. Conclusions: Targeted parallel sequencing of TG-related genes is recommended to define the molecular defect in children presenting with an incidental finding of HyperTG.

Original languageEnglish
JournalJournal of Clinical Lipidology
Publication statusAccepted/In press - 2017


  • APOA5
  • Familial chylomicronemia
  • Hypertriglyceridemia
  • LIPC and APOB genes
  • LPL
  • Targeted next-generation sequencing

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine


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