Wajdi Al-Shweiat, n/a
Dr.
Spectrum Health Lakeland, United States
Disclosure information not submitted.
Patrick McKillion, MD, FCCP
Dr.
Lakeland Medical Center Saint Joseph, United States
Disclosure information not submitted.
Title: ACETAMINOPHEN INDUCED PYROGLUTAMIC ACIDURIA LEADING TO SEVERE METABOLIC ACIDOSIS
Case Report Body:
Introduction: Pyroglutamic acid or 5-oxoproline accumulation is classically described as an inborn error of metabolism resulting from glutathione synthetase deficiency. Hemolytic anemia, episodic neutropenia, increased osmolar gap, and anion gap metabolic acidosis can be seen in adults with the acquired deficiency. We present a case of severe metabolic acidosis secondary to pyroglutamic acidosis after recent daily acetaminophen use.
Description: A 61-year-old female presented with altered mental status. She had a recent viral syndrome and decreased oral intake. She ingested 1000 mg of acetaminophen nightly for a week. Laboratory studies revealed hyperkalemia 7.8 mmol/L, metabolic acidosis (pH 6.97, HCO3- 2.4 mmol/L), increased anion gap 26 mEq/L, osmolar gap 29 mOsm/kg, normal lactate, and increased beta-hydroxybutyrate 2.69 mmol/L (0.02-0.27mmol/L). Despite an empiric sodium bicarbonate infusion, the patient underwent multiple hemodialysis treatments for refractory metabolic acidosis. Treatment included parenteral fomepizole and insulin infusion for potential toxic alcohol ingestion and normoglycemic DKA. Toxic alcohols, ethanol, and acetaminophen levels were normal. A urine organic acid screen was sent and initiated on empiric treatment with N-acetylcysteine. Her metabolic acidosis resolved. The organic acid screen demonstrated markedly elevated pyroglutamic acid (5-oxoproline) at 16741 mmol/mol.
Discussion: Chronic acetaminophen use saturates the glucuronide and sulfate metabolic pathways. This precipitates the accumulation of NAPBQI resulting in acquired glutathione deficiency. The deficiency creates an accumulation of pyroglutamic acid. As seen in this case, high anion gap metabolic acidosis in absence of common organic substances should raise the suspicion of pyroglutamic acidosis in the setting of chronic acetaminophen use. Fast recognition and prompt investigation of pyroglutamic acid level as well as early involvement of nephrologists could potentially shorten the patient ICU stay and improve patient clinical outcome.