Brief communication: Strong concordance of the North American Familial Chylomicronemia Syndrome Score with a positive genetic diagnosis in patients from the Balance study.

Abstract

Background: Patients with familial chylomicronemia syndrome (FCS) are often misdiagnosed. A positive genetic diagnosis is considered definitive, but clinical scoring systems can also identify affected patients. The North American FCS (NAFCS) Score is intended to identify patients likely to have positive DNA testing, but its sensitivity has not been quantified.

Objective: To evaluate NAFCS Scores in patients from the Balance study.

Methods: We calculated NAFCS Scores in 66 patients with genetically confirmed FCS from the Balance study of olezarsen.

Results: We found that 95.5% (63/66) and 74.2% (49/66) of patients had NAFCS Scores ≥45 ("likely FCS") and ≥60 ("definite FCS"), respectively. In contrast, no patient had a score <30 ("unlikely FCS"), while 4.5% (3/66) had scores between 30 and 44 ("uncertain FCS").

Conclusion: The strong concordance between NAFCS Score ≥45 and a positive genetic diagnosis of FCS suggests that either approach can be used for diagnosis except in "uncertain FCS" cases, which require genetic testing. The score might also clinically support an FCS diagnosis when genetic testing is indeterminate due to variants of unknown significance.