A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis, often manifesting in childhood. The condition results from variants in the lipoprotein lipase (LPL) gene, which lead to impaired fat metabolism. We report the case of an 18-year-old Saudi male with a lifelong history of hypertriglyceridemia and recurrent episodes of pancreatitis. Laboratory investigations revealed severe hypertriglyceridemia and low high-density lipoprotein cholesterol, consistent with FCS. A comprehensive evaluation excluded secondary causes of hyperlipidemia, suggesting a potential genetic basis for the condition. Whole-exome sequencing identified a novel homozygous missense variant (c.1307G>A; p.Gly436Glu) in the LPL gene. Bioinformatics analysis predicted this variant to be deleterious, potentially disrupting the structure and stability of the LPL enzyme and impairing its ability to hydrolyze dietary fats. This finding suggested a causal link between the variant and the patient's FCS phenotype. This case highlights the importance of molecular diagnosis in FCS, enabling the identification of causative genetic alterations and improving our understanding of the link between LPL dysfunction and severe metabolic disorders.