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Background: Activity assays for lipoprotein lipase (LPL) are not standardised for use in clinical settings. Objective: This study sought to define and validate a cut-off points based on a ROC curve for the diagnosis of patients with familial chylomicronemia syndrome (FCS). We also evaluated the role of LPL activity in a comprehensive FCS diagnostic workflow.

Methods: A derivation cohort (including an FCS group (n = 9), a multifactorial chylomicronemia syndrome (MCS) group (n = 11)), and an external validation cohort (including an FCS group (n = 5), a MCS group (n = 23) and a normo-triglyceridemic (NTG) group (n = 14)), were studied. FCS patients were previously diagnosed by the presence of biallelic pathogenic genetic variants in the LPL and GPIHBP1 genes. LPL activity was also measured. Clinical and anthropometric data were recorded, and serum lipids and lipoproteins were measured. Sensitivity, specificity and cut-offs for LPL activity were obtained from a ROC curve and externally validated.

Results: All post-heparin plasma LPL activity in the FCS patients were below 25.1 mU/mL, that was cut-off with best performance. There was no overlap in the LPL activity distributions between the FCS and MCS groups, conversely to the FCS and NTG groups.

Conclusion: We conclude that, in addition to genetic testing, LPL activity in subjects with severe hypertriglyceridemia is a reliable criterium in the diagnosis of FCS when using a cut-off of 25.1 mU/mL (25% of the mean LPL activity in the validation MCS group). We do not recommend the NTG patient based cut-off values due to low sensitivity.