BMJ Case Reports 2012; doi:10.1136/bcr.03.2012.6020
  • Rare disease

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

  1. Paul Ellis Marik2
  1. 1Department of Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA
  2. 2Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical school, Norfolk, Virginia, USA
  1. Correspondence to Dr Paul Ellis Marik, marikpe{at}


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.


  • Competing interests None.

  • Patient consent Obtained.

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