Key result
Clinical FCS diagnostic scores show high specificity but only ~74% sensitivity for genetically confirmed disease.
Why the study?
Two clinical scoring systems have been developed to identify familial chylomicronemia syndrome among individuals with severe hypertriglyceridemia, but their validation in molecularly defined patients was needed.
Do the European and North American FCS clinical diagnosis scores accurately identify familial chylomicronemia syndrome compared to genetic testing in patients with severe hypertriglyceridemia?
Cohort (n=237)
Do the European and North American FCS clinical diagnosis scores accurately identify familial chylomicronemia syndrome compared to genetic testing in patients with severe hypertriglyceridemia?
Both the European and North American clinical diagnosis scores for familial chylomicronemia syndrome have excellent specificity, but low sensitivity implies that genetic testing remains essential to avoid missed diagnoses.
Limited sensitivity of FCS scores may miss cases; leaves open need for genetic confirmation in severe hypertriglyceridemia.
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.
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Paquette et al. (2026) conducted a cohort in Severe hypertriglyceridemia and Familial chylomicronemia syndrome (FCS) (n=237). European and North American FCS (NAFCS) clinical diagnosis scores vs. Genetic confirmation was evaluated on Predictive performance for identification of genetically confirmed FCS. The European score (≥10) and NAFCS score (≥45) showed high specificity (97.0% and 99.0%) but limited sensitivity (74.3% for both) for identifying genetically confirmed familial chylomicronemia syndrome.
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