Understanding Updates in FCS Management with Newer Therapies

Familial chylomicronemia syndrome is a rare, severe inherited disorder of triglyceride metabolism characterized by an inability to clear chylomicrons due to biallelic loss-of-function mutations in genes critical for triglyceride clearance, most notably lipoprotein lipase. In this discussion, Nihar R. Desai, MD, describes the typical phenotype as marked hypertriglyceridemia—often with triglyceride levels in the 1000–2000 mg/dL range or higher—and recurrent acute pancreatitis with substantial morbidity and mortality. He emphasizes that, although many patients have elevated triglycerides, FCS represents a distinct and more extreme form of chylomicronemia that requires heightened clinical vigilance and timely diagnosis.

Anthony Giamo, MD, expands on the diagnostic framework by distinguishing genetically confirmed FCS from so‑called “functional” FCS, in which patients exhibit the full clinical phenotype despite negative genetic testing. He contrasts FCS with multifactorial chylomicronemia syndrome, noting that the latter is far more common and typically associated with comorbidities such as diabetes, obesity, and secondary factors, whereas FCS usually presents earlier in life in otherwise relatively healthy individuals. This differentiation is clinically important because FCS patients often have limited or no response to conventional triglyceride‑lowering treatments.

Both experts underscore that traditional therapies—including fibrates and omega‑3 fatty acids—frequently fail to meaningfully reduce triglycerides in FCS, leaving patients at persistent risk for recurrent pancreatitis. Desai highlights that therapeutic options have historically centered on a very low‑fat diet (<10% of caloric intake from fat) and alcohol avoidance, which are burdensome and often insufficient. Against this background, the faculty introduce the concept of newer targeted therapies capable of substantially lowering triglycerides in FCS, setting the stage for an evolving treatment paradigm built around APOC3‑directed agents and other novel approaches.