Accumulation of 5-oxoproline (pyroglutamic acid) has been reported as a rare cause of high anion gap metabolic acidosis. Chronic paracetamol ingestion in a susceptible individual can lead to accumulation of 5-oxoproline and a high anion gap metabolic acidosis. The condition resolves with supportive care and discontinuation of paracetamol and, most importantly, it can be prevented. This case report aims to alert clinicians to the condition as well as provide insight into the underlying mechanisms of the disease process. We report two cases of high anion gap metabolic acidosis due to accumulation of 5-oxoproline. Both patients had a recent history of regular paracetamol use for back pain on a background of poor nutrition. Common causes of high anion gap metabolic acidosis were excluded in both patients systematically. The underlying cause was discovered on testing for urinary 5-oxoproline. Both patients improved and the acidosis resolved upon withdrawal of paracetamol and other supportive measures. The need for a high index of suspicion and a detailed patient drug history is highlighted in these case reports, as raised anion gap metabolic acidosis is a common finding in critically ill patients. When lactate and ketones are absent, 5-oxoproline levels should be tested in patients who are taking paracetamol; especially in those who are malnourished or have other predisposing factors to reduced glutathione levels. Once suspected, paracetamol should be stopped, full supportive care should be initiated and treatment with N-acetylcysteine considered.
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