Work

Hemolysis and liver failure after acetaminophen ingestion in a patient with glutathione reductase deficiency

Year: 2026

Type: article

Abstract: Here we describe the case of a 47-year-old woman who developed severe hemolytic anemia, methemoglobinemia, acute liver injury, and acute kidney injury after acetaminophen ingestion. Although the clinical presentation initially suggested G6PD deficiency, enzyme testing was normal. Genetic evaluation instead identified a previously unreported homozygous missense mutation in the glutathione reductase gene (GSR; c.306C>G, p.Cys102Trp), resulting in markedly reduced enzyme expression and activity. Functional studies demonstrated impaired glutathione regeneration, increased oxidative stress, and enhanced red blood cell susceptibility to hemolysis. The patient recovered with supportive care, and treatment with N-acetylcysteine and vitamin C. This case highlights the critical role of glutathione reductase in acetaminophen detoxification and illustrates how rare defects in glutathione metabolism can mimic G6PD deficiency and precipitate life-threatening oxidative injury.

Source: Blood Red Cells & Iron

DOI: 10.1016/j.brci.2026.100111

Authors: John Schell, Jennifer Mead, Margaret Bouchard, Rachel Rosovsky, David B. Sykes

Institution: Mass General Brigham

Language: English

Topic: Drug-Induced Hepatotoxicity and Protection

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,000