J Clin Lipidol. 2026 Jul 10:S1933-2874(26)00433-2. doi: 10.1016/j.jacl.2026.07.012. Online ahead of print.
ABSTRACT
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia (sHTG) due to variants in canonical genes (LPL [lipoprotein lipase], APOA5, APOC2, GPIHBP1, and LMF1); its genotype distribution in Latin America remains scarcely reported. Given limited access to genetic testing and frequent negative results in clinically consistent cases, clinical scores and lipid ratios have been proposed to predict FCS.
OBJECTIVE: This study aimed to outline the genetic, clinical, and biochemical characteristics, as well as the performance of scoring systems, in a Latin American cohort of patients with sHTG.
METHODS: Genetic, clinical, and biochemical data were obtained in 77 individuals with sHTG (TG >10 mmol/L), including 28 genetically diagnosed FCS and 49 multifactorial chylomicronemia syndrome (MCS). Triglyceride/total cholesterol (TG/TC), TG/apolipoprotein B (apoB) ratios, and Moulin and North American Familial Chylomicronemia Score (NAFCS) scores were calculated.
RESULTS: Among patients with FCS, non-LPL monogenic defects were present in 64% of patients (n = 18), with variants in APOA5 (n = 11), GPIHBP1 (n = 3), APOC2 (n = 2), and LMF1 (n = 2). Diagnosis was frequently delayed, and body mass index overlapped across groups. Biochemical biomarkers showed good diagnostic performance, with AUCs of 0.767 (95% CI: 0.640-0.876; P < .0001) for TG/TC and 0.790 (95% CI: 0.651-0.906; P < .0001) for TG/apoB. Moulin score showed high sensitivity (91.3%), whereas NAFCS score showed high specificity (90.9%).
CONCLUSION: This large multicenter Latin American study of sHTG reveals a distinct genetic landscape from other regions. It also supports the performance of clinical scores and the discriminatory accuracy of biochemical indices.
PMID:42527267 | DOI:10.1016/j.jacl.2026.07.012