Acetaminophen-induced hepatotoxicity in a glutathione synthetase-deficient patient.
We report a patient with glutathione synthetase (GS) deficiency who developed acetaminophen-induced hepatotoxicity after a two-day treatment with regular doses of acetaminophen. A nine-month-old female was referred because of intractable metabolic acidosis. She was given acetaminophen at therapeutic doses over a 48-hour period. She was hospitalized because of confusion and metabolic acidosis. Liver function tests were abnormal with normal bilirubin levels. The urine gas chromatography-mass spectrometry (GC/MS) showed massive excretion of 5-oxoproline. She improved and liver function tests normalized in the next six days, but compensated metabolic acidosis and massive 5-oxoprolinuria persisted. The analysis of GS in erythrocytes revealed 5% of normal enzyme activity, and the patient had 491G > A mutation on both alleles in the GS gene. In this report it can be assumed that patients, even if heterozygous for a mutation of the GS gene, are at risk for acetaminophen toxicity.
Tokatli
Ayşegül
A
Unit of Nutrition and Metabolism, Department of Pediatrics, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
Kalkanoğlu-Sivri
H Serap
HS
Yüce
Aysel
A
Coşkun
Turgay
T
D000082:Acetaminophen / Q000009:adverse effects*; D000138:Acidosis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D005260:Female; D005981:Glutathione Synthase / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007223:Infant; D008111:Liver Function Tests
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D005981:Glutathione Synthase