ORF30-01 - Acute Pancreatitis Revealing Familial Chylomicronemia Syndrome in a Complex Metabolic Setting

Background
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis. Due to overlapping features with more common metabolic conditions, diagnosis is frequently delayed. Early recognition and rapid triglyceride reduction are essential to prevent morbidity and recurrent disease.

Case Presentation
A 42-year-old man with type 2 diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hypertension, asthma, and obesity presented with acute nausea and vomiting following a presumed foodborne illness. Laboratory evaluation revealed severe hypertriglyceridemia (triglycerides 3,754 mg/dL), elevated lipase, and imaging consistent with acute pancreatitis. Glycemic control was poor, with an HbA1c of 12.2%.

Medication review demonstrated inconsistent adherence to metformin, glipizide, empagliflozin/metformin XR, fenofibrate, and incretin-based therapy. The patient required intensive care unit admission and was treated with intravenous insulin infusion and fibrate therapy; however, triglyceride control remained challenging. Physical examination revealed eruptive xanthomas over the elbows.

Given the severity and refractory nature of hypertriglyceridemia, genetic testing was pursued and confirmed familial chylomicronemia syndrome due to an APOA5 mutation. Targeted therapy with olezarsen was subsequently initiated.

Discussion and Conclusion
This case highlights familial chylomicronemia syndrome as an important and underrecognized cause of acute pancreatitis, particularly in patients with poorly controlled diabetes and medication nonadherence. While no causal relationship can be established, the coexistence of severe genetic dyslipidemia and incretin-based therapy illustrates the clinical complexity encountered in high-risk metabolic phenotypes and underscores the need for individualized therapeutic assessment and close monitoring. Early diagnosis of FCS and timely initiation of emerging RNA-targeted therapies, such as olezarsen, are critical to preventing recurrent pancreatitis and improving long-term outcomes.