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

Robert A. Hegele, Western University, 1151 Richmond Street North, London, Ontario N6A 5B7, Canada. Electronic address: hegele@robarts.ca.
Zahid Ahmad, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9063, USA.
Ambika Ashraf, University of Alabama at Birmingham, 1600 7th Ave South, Birmingham, Alabama 35233-1771, USA.
Andrew Baldassarra, Western University, 1151 Richmond Street North, London, Ontario N6A 5B7, Canada.
Alan S. Brown, Advocate Health - MidwestFollow
Alan Chait, University of Washington, 850 Republican St., Mailstop 358062, Seattle, Washington 98109, USA.
Steven D. Freedman, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Suite Rabb Rose 1, Boston, Massachusetts 02215-5400, USA.
Brenda Kohn, New York University, 150 East 32nd St, 2nd Floor, New York, New York 10016, USA.
Michael Miller, Crescenz Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA; University of Pennsylvania, Translational Medicine and Human Genetics, 5th floor Silverstein Pavilion, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nivedita Patni, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9063, USA.
Daniel E. Soffer, University of Pennsylvania, Translational Medicine and Human Genetics, 5th floor Silverstein Pavilion, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Jian Wang, Western University, 1151 Richmond Street North, London, Ontario N6A 5B7, Canada.
Michael S. Broder, PHAR, 324 South Beverly Drive, Suite 350, Beverly Hills, California 90212, USA.
Eunice Chang, PHAR, 324 South Beverly Drive, Suite 350, Beverly Hills, California 90212, USA.
Irina Yermilov, PHAR, 324 South Beverly Drive, Suite 350, Beverly Hills, California 90212, USA.
Cynthia Campos, PHAR, 324 South Beverly Drive, Suite 350, Beverly Hills, California 90212, USA.
Sarah N. Gibbs, PHAR, 324 South Beverly Drive, Suite 350, Beverly Hills, California 90212, USA.

Affiliations

Advocate Lutheran General Hospital

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 context.

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

Methods:Using the RAND/UCLA modified Delphi process, we convened ten US/Canadian physicians with experience recognizing and treating FCS and one 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.

Type

Article

PubMed ID

39537503

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