Clinical identification of familial chylomicronemia syndrome and novel therapeutic options.

INTRODUCTION Hypertriglyceridemia (HTG) is a heterogeneous metabolic disorder driven by both genetic susceptibility and secondary factors. Most patients with severe HTG (triglyceride [TG] >10 mmol/L [>885 mg/dL]) have multifactorial chylomicronemia syndrome (MCS) while only a few have familial chylomicronemia syndrome (FCS), a rare autosomal recessive condition.

AREAS COVERED We summarize the pathophysiology of severe HTG, emphasizing impaired intravascular lipolysis of TG-rich lipoproteins and the regulatory role of apolipoproteins (apo), particularly apo C-III. We outline features that distinguish FCS from MCS and discuss diagnostic strategies, including clinical scoring systems and targeted genetic testing. Current management approaches, including responses to conventional TG-lowering therapies and emerging biologic therapies targeting apo C-III, are examined. We searched PubMed for all English language literature focusing on the search terms 'chylomicronemia,' 'familial chylomicronemia syndrome,' 'multifactorial chylomicronemia syndrome,' 'hypertriglyceridemia,' 'APOC3 inhibition,' 'antisense oligonucleotides,' and 'apolipoprotein C-III.'

EXPERT OPINION Differentiating FCS from MCS is critical because RNA-based inhibition of apo C-III has transformed the therapeutic landscape for FCS patients. These agents provide substantial, durable TG lowering, and meaningful reductions in pancreatitis risk, although cardiovascular benefit remains uncertain. Future efforts should focus on optimizing diagnostic pathways, assessing cardiovascular outcomes, and determining long-term safety of these novel biologic therapies.