Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America

Abstract

Background: Familial chylomicronemia syndrome (FCS) is an ultrarare inherited disorder. Genetic testing is not always feasible or conclusive. European clinicians developed a "FCS score" to differentiate between FCS and multifactorial chylomicronemia syndrome (MCS), a more common condition with overlapping features. A diagnostic score has not been developed for use in the North American (NA) context.

Objective: To develop and validate a diagnostic score for NA patients based on signs, symptoms and biochemical traits of FCS.

Methods: Using the RAND/UCLA modified Delphi process, we convened 10 US/Canadian physicians with experience recognizing and treating FCS and 1 adult patient with FCS. The panel developed and rated 296 scenarios describing patients with FCS. Linear regression analyses used median post-meeting ratings to develop score parameters. We tested the score's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in patients with classical FCS, functional FCS, and MCS from Western University's Lipid Genetics Clinic's registry.

Results: Numerical scores were attributed based upon the following: age, hypertriglyceridemia onset, body mass index, history of abdominal pain/pancreatitis, presence of secondary factors, triglyceride (TG) levels, ratio of TG/total cholesterol, and apolipoprotein B level. Scores ≥ 60 indicate definite classical FCS; the score distinguished patients with FCS from MCS in a real-world registry (100.0% specificity, 66.7% sensitivity, 100.0% PPV, 95.5% NPV). Scores ≥ 45 were "very likely" to have classical FCS (96.9% specificity, 88.9% sensitivity).

Conclusion: Given its simplicity and high specificity for distinguishing patients with FCS from MCS, the NAFCS Score could be used in lieu of - or while awaiting - genetic testing to optimize treatment.

Keywords: Delphi panel; Familial chylomicronemia syndrome; Hypertriglyceridemia; Lipoprotein lipase deficiency; Multifactorial chylomicronemia syndrome; Pancreatitis.