Multifactorial Chylomicronemia Syndrome With a Rare APOA5 Variant and Recurrent Acute Pancreatitis: A Case Report From Rural Colombia.

Source: PubMed, NCBI / U.S. National Library of Medicine

Severe hypertriglyceridemia (triglycerides ≥ 500 mg/dL) carries a high risk of recurrent acute pancreatitis and cardiovascular disease. Pathogenic variants in the APOA5 gene are associated with hyperlipoproteinemia type V and familial hypertriglyceridemia; however, detailed case reports involving variants of uncertain significance (VUS) with a severe clinical phenotype and documented therapeutic response are rarely published. A 46-year-old woman from rural Supía, Caldas, Colombia, presented with persistent very severe hypertriglyceridemia (peak: 2,170 mg/dL), three hospitalizations for acute pancreatitis, and inadequate response to statins and fibrates. Targeted exome sequencing identified a heterozygous APOA5 VUS: c.694T>C, p.Ser232Pro (NM_052968.5), classified as PM2/PP3 per ACMG criteria (ClinVar: VCV002617654.3). An off-label PCSK9 inhibitor regimen achieved a greater than 90% triglyceride reduction (nadir: 118 mg/dL), though adherence has been intermittent due to economic and healthcare access barriers. This case highlights the diagnostic value of targeted genetic testing in severe familial hypertriglyceridemia and illustrates how an APOA5 VUS may underlie a severe multifactorial chylomicronemia phenotype. Segregation analysis and functional studies in first-degree relatives are warranted to support variant reclassification. This report also underscores the impact of healthcare access barriers on rare metabolic disease outcomes in rural Latin America.