Genetic predisposition of Asparaginase-induced hypertriglyceridemia in children with acute lymphoblastic leukemia: Two case reports and review of literature.

BackgroundAsparaginase (ASP) is an essential antitumor agent of acute lymphoblastic leukemia (ALL) in children. Hypertriglyceridemia (HTG) represents one of several ASP-associated toxicities, alongside with hypersensitivity reactions, pancreatitis, liver dysfunction, and thrombotic events. HTG may necessitate immediate therapy modification and can lead to life-threatening complications that contraindicate further anticancer treatment. However, the clinical and genetic mechanisms underlying this condition remain poorly understood.Case summaryWe report two rare cases of severe HTG in pediatric patients with B-ALL following treatment with pegylated ASP (PEG-ASP). To investigate the genetic basis of this susceptibility, we performed genetic testing using a targeted gene panel for hyperlipidemia and identified several potential disease-related variants associated with inherited dyslipidemia. Although the functional and causal roles of these variants require further validation, we hypothesize that they contributed substantially to the development of HTG in these patients.ConclusionGenetic factors may predispose to HTG during PEG-ASP therapy; with further evidence, genetic testing might be considered before ASP treatment.