Introduction: Pyroglutamic acid (5-oxoproline) is an intermediate in the γ-glutamyl cycle necessary for glutathione synthesis and its toxicity is a rare cause of high anion gap metabolic acidosis (HAGMA). Toxicity is often primarily associated with chronic acetaminophen use (>10 days) especially in patient who have other comorbid conditions such as malnourishment, sepsis, renal dysfunction, or chronic illnesses. The reduction in glutathione and impaired metabolism of pyroglutamic acid due to acetaminophen leads to increased accumulation of pyroglutamic acid.
Description: A 67-year-old woman with a history of uterine cancer status post total hysterectomy and chemo/radiation therapy initially presented to the hospital from the infectious disease clinic after one week of generalized malaise requiring further evaluation. She was found to have candidemia requiring a prolonged course of micafungin, however due to social drivers of health she remained hospitalized receiving 1000mg acetaminophen every 6 hours for 3 weeks. Due to her history of chronic acetaminophen use, prolonged illness requiring hospitalization, severe malnutrition evidenced by an albumin of 1.7 g/dL and total protein 3.4 g/dL pyroglutamic acidosis was suspected as a contributing factor to her high anion gap metabolic acidosis. Acetaminophen was discontinued, she was initiated on N-acetylcysteine and given bicarbonate infusion for management of concomitant hyperkalemia with severe lactic acidosis. Patient required CVVHD due to life threatening hyperkalemia and worsening renal function; however, her condition deteriorated, and she passed away within five days of diagnosis.
Discussion: Pyroglutamic acid is one of the rare causes of HAGMA. Suspicion should be risen in patients with HAGMA and lactic acidosis who have prolonged acetaminophen use, chronic illness, malnutrition, or renal dysfunction as they are at high risk due to glutathione depletion and dysregulation of the γ-glutamyl cycle. Patients often have a nonspecific presentation including, but not limited to, nausea, vomiting, kussmaul respirations, or altered mental status. This case highlights the importance of maintaining a high index of suspicion for 5-oxoproline acidosis in critically ill patients with unexplained metabolic acidosis.
