Unmasking a Rare Genetic Mutation: The Importance of Genetic Testing in Refractory Hypertriglyceridemia

Background/objective: Genetic causes of hypertriglyceridemia like familial chylomicronemia syndrome can be overlooked in everyday practice. We report a patient with a rare genetic mutation, highlighting the importance of genetic testing for timely diagnosis and prevention of complications.

Case report: A 45-year-old Hispanic female presented with serum triglyceride levels of 749 mg/dL, refractory to rosuvastatin 10 mg daily and omega-3 ethyl esters 2 g daily. Initial studies showed total cholesterol of 278 mg/dL and high-density lipoprotein of 38 mg/dL. Physical examination was negative for hepatosplenomegaly and xanthoma, with no reported history of acute pancreatitis. Despite treatment escalation with gemfibrozil, fenofibrate, and icosapent ethyl, her triglyceride levels remained elevated, peaking at 4300 mg/dL. Seven years after presentation, genetic testing revealed homozygosity for c.11delC of the apolipoprotein A5 gene, confirming the diagnosis of familial chylomicronemia syndrome. Postdiagnosis, the patient adhered to a strict low-fat diet with daily fat intake of less than 15-20 g, limited simple sugars, refined carbohydrates, and alcohol, leading to a nadir of serum triglycerides of 197 mg/dL.

Discussion: The identified mutation is exceedingly rare (<0.01%), as most associated mutations involve the lipoprotein lipase gene. There are no approved therapies for genetic hypertriglyceridemia. The mainstay of treatment is a very low-fat diet to prevent complications.

Conclusion: We underscore the importance of genetic testing in refractory hypertriglyceridemia despite a lack of clinical signs. A definitive diagnosis can alleviate patient burden, improve therapeutic adherence, and enhance the patient-physician relationship.