A case report of hyperchylomicronemia and recurrent pancreatitis in a patient with the pArg333His variant of the lipoprotein lipase gene

Abstract

Background/Synopsis

A 69-year-old African American male with severe hypertriglyceridemia, hyperchylomicronemia (> 4,000), and recurrent pancreatitis associated with the p.Arg333His variant of the Lipoprotein Lipase (LPL) gene. The patient did not respond to multiple triglyceride-lowering medications and continued to experience recurring episodes of pancreatitis. Severe hypertriglyceridemia, poor response to pharmacologic therapy, and history of recurrent pancreatitis prompted consideration of primary chylomicronemia. Genetic testing identified two single nucleotide variants of the LPL gene: p.Arg333His and a rare variant of unknown significance (VUS), p.His71Gln. Dietary control, collaboration with a nutritionist, and Orlistat have been successful.

Objective/Purpose

Show the correlation of likely pathogenic multivariant genes and the intersectionality of environmental factors’ roles in severe hypertriglyceridemia.

Methods

Due to the severity of the hypertriglyceridemia, we conducted cascade screening and genetic testing for the patient and family.

Results

Genetic testing identified the pathogenic pArg333His variant of the LPL gene, along with a 92nd percentile polygenic risk score for hypertriglyceridemia in the proband, resulting in a diagnosis of multifactorial chylomicronemia syndrome (MCS). A second variant of the LPL gene (p.His71Gln) was observed, and cascade screening revealed that this and the pathogenic gene variant were carried on different LPL gene alleles in the proband (compound heterozygote). A family member carrying only the p.His71Gln gene variant was found to have moderate hypertriglyceridemia despite a low polygenic risk score for hypertriglyceridemia.

Conclusions

Genetic testing identified a pathogenic variant LPL gene combined with a high polygenic risk score for hypertriglyceridemia, which led to the diagnosis of multifactorial hyperchylomicronemia. Cascade screening suggested the second LPL gene variant (p.His71Gln) in biallelic configuration to the pathogenic p.Arg333His variant contributed to the severity of the patient's hypertriglyceridemia. The genetic findings guided the treatment referral to a nutritionist, a 10-15% fat-restricted diet, and adherence to Orlistat, which inhibits fat absorption. The patient has maintained triglyceride levels below 400 mg/dL and no further episodes of pancreatitis. The novel p.His71Gln variant warrants further investigation to clarify its role in the pathogenesis of multifactorial chylomicronemia syndrome.