Novel pathogenic variant combination in causing familial chylomicronemia syndrome in an Asian family and experimental validation : a case report.

BACKGROUND

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder, typically caused by biallelic pathogenic variants in the lipoprotein lipase () gene. Lipoprotein lipase, encoded by the gene, catalyzes the hydrolysis of triglycerides, and its deficiency or dysfunction can lead to chylomicronemia and potentially fatal recurrent acute pancreatitis.

CASE DESCRIPTION

Here, we report an Asian child with FCS due to compound heterozygous variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. experimental validation found that the p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the p.L263Q variant mainly impaired its lipolytic activity.

CONCLUSIONS

FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. experiments showed that the two variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.