Highlights
- •FCS is a rare genetic disorder that results in LPL activity deficiency.
- •The LPL activity method is not standardised.
- •Cut-off points to consider LPL activity deficiency must be stablished.
- •A cut-off value of 25 % of the mean LPL activity of a MCS cohort has been defined.
- •A comprehensive workflow for FCS diagnosis is provided in this study.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: January 25, 2023
Accepted:
January 18,
2023
Received:
September 16,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.
