Chronic acetaminophen ingestion resulting in severe anion gap metabolic acidosis secondary to 5-oxoproline accumulation: an under diagnosed phenomenon

BMJ Case Rep. 2012 Jul 3;2012:bcrbcr0320126020. doi: 10.1136/bcr.03.2012.6020.


Anion gap metabolic acidosis is commonly caused by lactic acidosis, ketoacidosis, and ingestion of methanol, salicylates, ethylene glycol or accumulation of organic/inorganic acids. However, rare causes of metabolic acidosis from enzyme defects, such as disturbances in the γ-glutamyl cycle, are being reported in higher frequencies in the adult population. Such disturbances cause an accumulation of 5-oxoproline and ultimately an anion gap metabolic acidosis. These disturbances are often associated with acetaminophen in the setting of certain risk factors such as sepsis, malnutrition, liver disease, female gender, pregnancy or renal failure.

Publication types

  • Case Reports

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Acetaminophen / pharmacokinetics
  • Acid-Base Equilibrium / drug effects
  • Acidosis, Lactic / blood
  • Acidosis, Lactic / diagnosis*
  • Acidosis, Lactic / etiology
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Chronic Disease
  • Diagnosis, Differential
  • Dose-Response Relationship, Drug
  • Eating
  • Female
  • Humans
  • Middle Aged
  • Pregnancy
  • Pyrrolidonecarboxylic Acid / blood*
  • Severity of Illness Index


  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Pyrrolidonecarboxylic Acid