Frontiers in Genetics (Feb 2022)

Case Report: Genetic Analysis of PEG-Asparaginase Induced Severe Hypertriglyceridemia in an Adult With Acute Lymphoblastic Leukaemia

  • Arcangelo Iannuzzi,
  • Mario Annunziata,
  • Giuliana Fortunato,
  • Carola Giacobbe,
  • Daniela Palma,
  • Alessandro Bresciani,
  • Emilio Aliberti,
  • Gabriella Iannuzzo

DOI
https://doi.org/10.3389/fgene.2022.832890
Journal volume & issue
Vol. 13

Abstract

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PEG-Asparaginase (also known as Pegaspargase), along with glucocorticoids (predominantly prednisolone or dexamethasone) and other chemotherapeutic agents (such as cyclophosphamide, idarubicin, vincristine, cytarabine, methotrexate and 6-mercaptopurine) is the current standard treatment for acute lymphoblastic leukaemia in both children and adults. High doses of PEG-asparaginase are associated with side effects such as hepatotoxicity, pancreatitis, venous thrombosis, hypersensitivity reactions against the drug and severe hypertriglyceridemia. We report a case of a 28-year-old male who was normolipidemic at baseline and developed severe hypertriglyceridemia (triglycerides of 1793 mg/dl) following treatment with PEG-asparaginase for acute lymphoblastic leukaemia. Thorough genetic analysis was conducted to assess whether genetic variants could suggest a predisposition to this drug-induced metabolic condition. This genetic analysis showed the presence of a rare heterozygous missense variant c.11G > A-p.(Arg4Gln) in the APOC3 gene, classified as a variant of uncertain significance, as well as its association with four common single nucleotide polymorphisms (SNPs; c.*40C > G in APOC3 and c.*158T > C; c.162-43G > A; c.-3A > G in APOA5) related to increased plasma triglyceride levels. To our knowledge this is the first case that a rare genetic variant associated to SNPs has been related to the onset of severe drug-induced hypertriglyceridemia.

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