Whole Exome Sequencing Identifies Three Novel Gene Mutations in Patients with the Triad of Diabetic Ketoacidosis, Hypertriglyceridemia and Acute Pancreatitis

Background: This study aimed to analyze the genetics and treatments of the patients with the triad of diabetic ketoacidosis (DKA), hypertriglyceridemia and acute pancreatitis (AP).

Methods: We conducted a retrospective study of six patients with the triad of AP, hypertriglyceridemia and DKA at our hospital. All patients underwent plasmapheresis as part of their treatment. The clinical characteristics of the patients were obtained from the hospital information system and analyzed. Whole exome sequencing was performed using samples of one patient (case 6) and his family members.

Results: The average triglyceride level before plasmapheresis was 3282.17 ± 2975.43 mg/dL (range: 1646-9332 mg/dL). The triglyceride levels dropped by approximately 80% after plasmapheresis. None of the patients developed complications related from plasmapheresis. During follow-up, patients 5 and 6 developed recurrent pancreatitis for several times, and showed the formation of pancreatic pseudocysts. We identified three novel heterozygous missense mutations in the family of patient 6, including c.12614C>T (p.Pro4205Leu) in APOB, c.160G>C (p.Glu54Gln) in CILP2, and c.1199C>A (p.Ala400Glu) in PEPD.

Conclusions: Three novel heterozygous missense mutations, including c.12614C>T (p.Pro4205Leu) in APOB, c.160G>C (p.Glu54Gln) in CILP2, and c.1199C>A (p.Ala400Glu) in PEPD were first identified in a patient with the triad of DKA, hypertriglyceridemia and AP. The combination of plasmapheresis, hydration and insulin therapy may have the greatest clinical benefits for these patients.

Keywords: acute pancreatitis; diabetic ketoacidosis; hypertriglyceridemia; whole exome sequencing.