Validation of two familial chylomicronemia syndrome clinical diagnosis scores in a cohort of molecularly defined patients.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of triglyceride metabolism associated with an extremely high lifetime risk of acute pancreatitis. Two clinical scoring systems have been developed to identify these patients with FCS among individuals with severe hypertriglyceridemia. OBJECTIVE: To validate the European and the North American FCS (NAFCS) scores in a cohort of molecularly defined patients with severe hypertriglyceridemia. METHODS: A total of 35 FCS and 202 patients with non-FCS were included in this retrospective study. Diagnostic accuracy measures (sensitivity, specificity, positive predictive value, and negative predictive value) and areas under the receiver operating characteristic curves were calculated to evaluate the predictive performance of the FCS scores. RESULTS: A European score ≥10 was associated with a sensitivity of 74.3% and a specificity of 97.0% for the identification of genetically confirmed FCS. The NAFCS score at a threshold of 45 (likely FCS) showed a similar but slightly better performance with a sensitivity of 74.3% and a specificity of 99.0%. The definite FCS threshold of the NAFCS score (≥60) was associated with a much lower sensitivity (37.1%) and a perfect specificity (100.0%). CONCLUSION: We provide one of the largest external validations for both the European score and the NAFCS score. We demonstrated that these scores have a very good specificity for minimizing false positives. However, a substantial proportion of patients with FCS are missed using these scores, resulting in missed opportunities for treatment and suggesting that genetic testing remains essential to confirm the diagnosis.