Application of the North American Familial Chylomicronemia Syndrome Score (NAFCS Score) in monogenic...

Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosomal recessive disorder of chylomicron metabolism known as Familial Chylomicronemia Syndrome (FCS). Due to the risk of recurrent acute pancreatitis and subsequent pancreatic insufficiency, early and accurate diagnosis of FCS is clinically critical. Although genetic testing is considered the gold standard for diagnosis, access remains limited in many settings. To address this gap, the North American Familial Chylomicronemia Syndrome score (NAFCS Score) has been developed as a clinical tool incorporating readily available clinical and biochemical parameters. This study aimed to evaluate the performance of the NAFCS score in a cohort of genetically confirmed FCS patients.

A total of 38 patients with genetically confirmed biallelic mutations causing FCS were evaluated retrospectively. Data on demographics, comorbidities, laboratory values, and pancreatitis history were collected. NAFCS was applied to each patient, and concordance between the score categories and the genetic diagnosis was assessed descriptively.

Among 38 genetically confirmed FCS patients, 52.6% were female. The median age was 35 years (IQR: 27-48 years). Acute pancreatitis had occurred in 86.8% of cases. The median triglyceride level was 3523 mg/dL (IQR: 2553-4470 mg/dL), and the median NAFCS was 65 (IQR: 52-81); 65.8% scored ≥60, 18.4% scored 45 to 59, and 15.8% scored <45.

The use of the NAFCS may serve as a useful tool in the differential diagnosis of patients with limited access to genetic testing. In this cohort, 84.2% of patients scored ≥45, the proposed threshold suggestive of a likely or definite diagnosis of FCS. This highlights the clinical utility of the scoring system in cases with HTG.