Variants APOA5 p.G185C and p.S19W associated with early-onset severe hypertriglyceridemia-induced pancreatitis and diabetes complications in a Vietnamese girl

Abstract

An imbalance of glucose and severely high triglyceridesare the key characteristics driving hypertriglyceridemia and hyperlipidemic pancreatitis. Hereditary factors considerably promote the increase of triglyceride levels and secondary complications. This study explored the clinical characteristics and geneticcauses of a young girl with recurrent severe hypertriglyceridemia-developed pancreatitis at 9years oldand diabetes mellitus appearance at 14yearsold. At 20 years old, she was admitted to the hospital in critical condition and had pancreatitis with a triglyceride level of26.22 mmol/L, HbA1c level of 15%, and a glucose level of 21.3 mmol/L. Whole exome sequencing analysis showed that she had compound heterozygous variants, p.G185C and p.S19W, in the APOA5gene, which werereported as risk factors for hypertriglyceridemia, and other variantsof uncertaintyin the APOEand CFRTgenes. The results and analysis proposethatthese variations were the underlying causes of elevated plasma triglycerides and led to the onset of metabolic complicationsat a juvenile age. These findings shed light on the molecular mechanism of elevated plasma triglyceride and the early onset of diabetes following hyperlipidemic pancreatitis in the patient.