Case ReportSevere Anion Gap Metabolic Acidosis From Acetaminophen Use Secondary to 5-Oxoproline (Pyroglutamic Acid) Accumulation
Section snippets
CASE 1
A 19-year-old woman without any significant medical history presented to her local emergency department (ED) 20 hours after ingesting 225 tablets of 500 mg of acetaminophen (total dose of 112.5 g). The patient’s plasma acetaminophen level at the local ED was elevated at 216 μg/L (reference range < 50 μg/L). Arterial blood gas (ABG) results showed a pH of 7.0, of 133 mm Hg, of 18 mm Hg and HCO3 of 4 mmol/L. Aspartate aminotransferase was elevated at 475 U/L (8–43 U/L) and alanine aminotransferase
CASE 2
A 67-year-old woman with multiple comorbidities, including a long-standing history of alcohol abuse, alcoholic cirrhosis, chronic pancreatitis, recurrent cholecystitis and recurrent gastrointestinal (GI) bleeding, was admitted to the hospital for a severe GI bleed. The diagnostic workup revealed a GI stromal tumor that was resected surgically. Postoperatively on hospital day 4, she was started on oral acetaminophen (1000 mg every 6 hours). Her hospital course was complicated by acute wound
DISCUSSION
5-Oxoproline also known as pyroglutamic acid is an uncommon cause of severe AGMA and is often overlooked. 5-Oxoproline is a strong organic acid that readily dissociates upon formation8 and results in generation of hydrogen anion. It is a derivative of amino acids and has a similar composition to glutamic acid, except that it has a cyclic form.8 It is an intermediate metabolite of γ-glutamyl cycle, a cycle involved in transport of amino acids into the cells.
The γ-glutamyl cycle starts with the
CONCLUSION
5-Oxoproline accumulation after acetaminophen ingestion is a rare but important cause of AGMA. In 2008, a new mnemonic for AGMA known as GOLD MARK was proposed21 and stands for: glycols (ethylene and propylene), oxoproline, l-lactate, d-lactate, methanol, aspirin, renal failure and ketoacidosis. We encourage physicians to consider using this mnemonic as it takes into account all the important causes of AGMA encountered in this contemporary era of clinical practice.
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2017, Clinica Chimica ActaCitation Excerpt :The level of pyroglutamate is often used to screen for glutathione synthetase deficiency in pediatric patients [23]. Children with deficiencies of either glutathione synthase or 5-oxoprolinase will present with metabolic acidosis or other abnormalities due to the accumulation of pyroglutamic acid [24–26]. When glycine is insufficiently available to support glutathione recovery via the renal gamma-glutamyl cycle, the rising level of pyroglutamate is regarded as an index of glycine insufficiency.
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