title: 5-oxoprolinemia causing elevated anion gap metabolic acidosis in the setting of acetaminophen use.
abstract: BACKGROUND
  Anion gap metabolic acidosis is typically encountered in the emergency department (ED) setting as the result of shock, other endogenous metabolic derangements, or from exogenous toxicants. The differential diagnosis for toxicant-related acidosis (exemplified by common mnemonics) emphasizes acute overdose.
  
  
  METHODS
  The case we present manifested an anion gap (AG) metabolic acidosis due to a chronic intoxication: acetaminophen (APAP) overuse over a period of weeks. Lactic acidemia did not account for the AG. In this case, chronic APAP overuse, combined with decreased caloric intake and weight loss, was associated with excess 5-oxoproline (pyroglutamic acid), an organic acid accounting for the AG metabolic acidosis. Overproduction of 5-oxoproline is attributed to depleted glutathione stores, leading to perturbation in the γ-glutamyl cycle. The patient was treated with supportive care and with N-acetylcysteine (NAC). By repleting glutathione, NAC may facilitate the resolution of excess 5-oxoproline.
  
  
  CONCLUSIONS
  The ED differential diagnosis of AG metabolic acidosis in chronic APAP overuse, especially with concomitant nutritional compromise, should include 5-oxoprolinemia.
authors: Division of Clinical Pharmacology, California Poison Control System, San Francisco Division, San Francisco, California, USA.
authors: Patil
authors: P
authors: Armenian
authors: Roy R
authors: RR
authors: Gerona
authors: Paul D
authors: PD
authors: Blanc
authors: Alan H B
authors: AH
authors: Wu
authors: Somnath
authors: S
authors: Mookherjee
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000209:etiology*; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005981:Glutathione Synthase / Q000172:deficiency; D006801:Humans
chemical_list: D018712:Analgesics, Non-Narcotic; D016166:Free Radical Scavengers; D000082:Acetaminophen; D005981:Glutathione Synthase; D000111:Acetylcysteine