Senior Director of Operation ECOGENE-21 Chicoutimi, Quebec, Canada
Background: Persistent chylomicronemia (PC) is associated with elevated acute pancreatitis risk and triglycerides (TG) level >10 mmol/L in >50% of multiple TG measurements despite the use of conventional TG-lowering treatment and control of secondary causes. Familial chylomicronemia syndrome (FCS) is a rare cause of PC affecting biallelic carriers of pathogenic variants in the the lipoprotein lipase gene (LPL) machinery (biallelic FCS) or patients presenting FCS characteristics but lacking genetic confirmation (clinical FCS). However, most patients with PC are not affected by FCS but present multifactorial chylomicronemia (persistent MCS). Diagnosis scoring systems have been developped to help differentiate FCS from MCS patients. The objective of this study was to assess the performance of three diagnosis scoring systems for the differential diagnosis of the various PC phenotypes.
METHODS AND RESULTS:
Methods: This study included 413 adults with chylomicronemia among which 348 non-persistent MCS, 39 biallelic FCS, 15 clinical FCS and 11 persistent MCS. FCS-causing genes were sequenced in all PC patients. Scores were calculated for all patients using the French-Canadian (A), the European (B) and the North American (C) FCS scoring systems. Cut-off values used for FCS diagnosis were ≥9 (model A), ≥10 (model B), ≥60 and ≥45 (model C). Statistical analyses were performed using Stata/MP (College Station, TX, USA).
Results: Patients with persistent MCS usually have lower scores than FCS, but higher than non persistent MCS, and are most often not identified by using FCS diagnosis scoring systems. FCS diagnosis scoring systems fairly identify FCS patients without discriminating biallelic FCS from clinical FCS. Models A and B presented similar performance (specificity [95%CI]: 0 [0 – 22] and 20 [4 – 48.1]; sensitivity: 100 [91-100] and 97 [86-100], respectively). Model C showed very high specificity (100 [78-100]) but relatively low sensitivity (64 [47-79]) with cut-off cut-off ≥60. However it showed result more similar to models A and B with cut-off ≥45 (specificity: 40 [16-68]); sensitivity: 92 [79-98]).
Conclusion:
Conclusion: FCS diagnosis scoring systems fairly identify FCS patients without discriminating biallelic FCS from clinical FCS. Persistent MCS represents a health burden and an unmet medical need that should be considered similarly to FCS with respect to access to LPL-independent therapies.
