Case Presentation: Pyroglutamic acid (5-oxoproline) is a rare cause of metabolic acidosis most often associated with sub-acute or chronic acetaminophen intake in the presence of unique risk factors.
Discussion: A 25-year old female with Crohn’s disease presented with one month of worsening abdominal pain, diarrhea, and anorexia with reported 20 kg weight loss. She developed septic shock secondary to sigmoid colon perforation and underwent sub-total colectomy and end-ileostomy. Her hospital course was complicated by stage 2 acute kidney injury (AKI) secondary to acute tubular necrosis with a peak creatinine of 0.8 mg/dL from baseline of 0.3 mg/dL. Her AKI gradually resolved with supportive treatment. Over a 10-day period, she received a total of 20 g of acetaminophen with a total daily dose <4 g/day. Subsequently, a persistent unexplained high-anion gap metabolic acidosis developed with serum bicarbonate levels as low as 11 mmol/L and a corrected anion gap of 26 mmol/L. Further laboratory data showed normal serum osmolality, blood urea nitrogen, beta-hydroxybutyrate, L-lactate, D-lactate, acetaminophen, and salicylate levels. Upon subsequent investigation, a urine 5-oxoproline level was markedly elevated at 26,740 mmol/mol creatinine. The patient's severe metabolic acidosis resolved with discontinuation of acetaminophen and oral bicarbonate supplementation.
Conclusions: Pyroglutamic acidosis is an often underrecognized condition requiring a high index of clinical suspicion for diagnosis. Urine or serum 5-oxoproline levels are needed for diagnosis, which may not always be readily available. Chronic acetaminophen use depletes intracellular glutathione resulting in increased levels of 5-oxoproline. Patients, like the one reported here, with malnutrition, female gender, sepsis, and kidney dysfuction are especially susceptible as they have lower glutathione levels leading to faster 5-oxoproline accumulation despite standard dosing of acetaminophen. Prompt recognition is essential for treatment with acetaminophen cessation and bicarbonate supplementation. The use of acetaminophen as an analgesic alternative to opioids is growing, especially in peri-operative and critical care settings. Clinical awareness of predisposing conditions and close monitoring of patient’s acid-base and kidney status can help us mitigate this underrecognized complication of acetaminophen use.