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

Authors

Alan S. Brown, Advocate Health - MidwestFollow
Philippe Moulin, Department of Endocrinology, Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, INSERM UMR 1060 CARMEN, Lyon, France, (Dr Moulin).
Andrew Dibble, Ionis, Carlsbad, CA, USA, (Drs Dibble, Alexander, Li, Tsimikas).
Veronica J. Alexander, Ionis, Carlsbad, CA, USA, (Drs Dibble, Alexander, Li, Tsimikas).
Lu Li, Ionis, Carlsbad, CA, USA, (Drs Dibble, Alexander, Li, Tsimikas).
Daniel Gaudet, Department of Medicine, University of Montréal and Ecogene-21, Chicoutimi, QC, Canada, (Dr Gaudet).
Joseph L. Witztum, Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA, USA, (Dr Witztum).
Sotirios Tsimikas, Ionis, Carlsbad, CA, USA, (Drs Dibble, Alexander, Li, Tsimikas); Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA, (Dr Tsimikas).
Robert A. Hegele, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, (Dr Hegele); Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, (Dr Hegele). Electronic address: hegele@robarts.ca.

Recommended Citation

Brown AS, Moulin P, Dibble A, et al. Brief communication: Strong concordance of the North American Familial Chylomicronemia Syndrome Score with a positive genetic diagnosis in patients from the Balance study. J Clin Lipidol. 2025;19(5):1451-1456. doi:10.1016/j.jacl.2025.07.008

Affiliations

Advocate Lutheran General Hospital

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

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.

Type

Article

PubMed ID

40841240