Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder caused by biallelic loss-of-function mutations in genes involved in chylomicron metabolism, most commonly lipoprotein lipase (LPL). Impaired intravascular lipolysis results in persistent fasting hypertriglyceridaemia, typically >10 mmol/L, and a lifelong risk of recurrent pancreatitis. Unlike multifactorial chylomicronemia, FCS is typically unresponsive to statins, fibrates, niacin, and PCSK9 inhibitors, which act via hepatic lipid pathways rather than chylomicron metabolism.
We present the case of a 60-year-old Indigenous woman with recurrent hypertriglyceridaemia-associated pancreatitis. Despite maximal tolerated medical therapy, including rosuvastatin/ezetimibe, fenofibrate, strict dietary fat restriction, and insulin, her triglycerides remained severely elevated (25.8–64 mmol/L). HDL levels were consistently low (0.5 mmol/L), and LDL levels could not be accurately measured due to lipaemic interference. Glycaemic control was suboptimal (peak HbA1c 13.5%) and likely exacerbated her metabolic dysregulation. A clinical diagnosis of FCS was made in 2023 following review in a specialist lipid clinic.
During a hospital admission in 2025 for severe pancreatitis (TG 49.9 mmol/L, lipase 288 U/L), the patient underwent inpatient plasmapheresis, with consideration of outpatient therapeutic plasma exchange for long-term management. PCSK9 inhibitors were not pursued due to mechanistic ineffectiveness in FCS.
This case highlights the therapeutic challenges of managing FCS. While insulin and plasmapheresis may offer temporary reductions in triglyceride levels, long-term control remains difficult. Novel therapies targeting APOC3, such as volanesorsen, olezarsen and plozasiran, have shown promise in reducing triglycerides and pancreatitis risk but remain largely inaccessible in Australia.
Strict dietary fat restriction remains the foundation of long-term management. Early recognition and referral to lipid clinics are essential to optimise care and facilitate access to emerging treatments in this high-risk population.