PYROGLUTAMIC ( 5 - OXOPROLINE ) ACIDOSIS: Uncommon cause of HAG metabolic acidosis

▪ Decreased glutathione store, increased activity of gamma glutamyl cyclotransferase is increased, key enzyme in gamma glutamyl cycle. This results in pyroglutamic (oxoproline) acid accumulation.

▪ Conditions associated:
      -Chronic paracetamol use
      -Chronic ethanol abuse
      -Malnutrition
      -Pregnancy
      -Congenital enzyme deficiency
      -Hepatic and renal impairment
      -Sepsis
      -Drugs: Flucloxacillin, Netilmycin, Vigabatrin

▪80 Y F presents in ER with lethargy and dizziness. Past medical history revealed chronic back pain treated with paracetamol and ibuprofen. She also takes ramipril for Hypertension. Examination suggested chronically ill, arousal and awake patient. BP 150/65, HR 72, RR 32, SPO2 98% on room air. Other systemic examination was unremarkable.
Lab revealed normal CBC , Na 138, K 3.6, Cl 98, HCO3 9, lactate 1.2, Glucose132, AST 65, ALT 75, Normal ammonia, BUN 30, Creatinine 1.5. Toxicology result showed acetaminophen level less than 10, negative salicylate and ethanol level.
Patient was managed conservatively. Anion gap closed and metabolic acidosis improved in 48 hours. Renal function also improves.
Review of past history revealed similar episodes 5 months back, which also resolved after 2 days of hospital admission.

▪Diagnosis: Ruling out other causes of HAG metabolic acidosis, serum/ urine 5 oxoproline level.
5 oxoproline level is not readily available, therefore PYROGLUTAMIC acidosis should be suspected in a patient with no explainable cause for HAG metabolic acidosis, and conditions predisposing to glutathione deficiency.

▪Management: 5 oxoproline is water soluble. IV fluid and diuresis leads to rapid resolution in 24-48 hours.
Of course correction/ removal of factor leading to glutathione store depletion is important requisite for prevention.
No acetycysteine also aids in management by repletion of glutathione store.

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