Eur J Pediatr DOI 10.1007/s00431-015-2585-6
CASE REPORT
Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant Sarah L. Hulley 1 & Jeff Perring 1 & Nigel Manning 1 & Simon Olpin 1 & Sufin Yap 1
Received: 22 April 2015 / Revised: 15 June 2015 / Accepted: 18 June 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Transient 5-oxoprolinuria is a phenomenon that is well recognised in adults. We illustrate an unusual paediatric case of transient 5-oxoprolinuria presenting during an episode of severe sepsis with concomitant paracetamol use. The 15month-old patient had an extremely high anion gap metabolic acidosis. Adequate resuscitation failed to correct the biochemical disturbance, and high levels of 5-oxoproline were identified. A combination of haemofiltration, replenishment of glutathione stores with N-acetylcysteine and cessation of paracetamol administration resulted in the resolution of the acidosis. Subsequent testing following treatment of the sepsis revealed no ongoing 5-oxoprolinuria. Conclusion: Transient 5-oxoprolinuria has been previously reported in the adult population during episodes of severe sepsis and various pharmaceutical interventions. This case illustrates that it is a phenomenon that should be considered in paediatric patients where a very high anion gap metabolic acidosis exists that cannot be explained by the biochemical indices.
What is Known: • 5-oxoprolinuria in the paediatric population is usually secondary to an inborn error of metabolism. • Transient 5-oxoprolinuria is well recognised in adults during episodes of severe glutathione depletion. What is New: • Transient 5-oxoprolinuria is a phenomenon rarely reported in the paediatric population. • It highlights the importance of investigating a high anion gap such that unusual diagnoses are not missed.
Keywords Anion gap . Metabolic acidosis . 5-oxoproline . Paracetamol . Pyroglutamate
Abbreviations CRP C-reactive protein MA Metabolic acidosis NAPQI N-acetylbenzoquinoneimine
Communicated by Beat Steinmann * Sufin Yap [email protected] Sarah L. Hulley [email protected] Jeff Perring [email protected] Nigel Manning [email protected] Simon Olpin [email protected] 1
Sheffield Children’s NHS Foundation Trust, Sheffield Children’s Hospital, Western Bank, Sheffield S10 2TH, UK
Introduction Hypovolaemia and hypoxia are relatively common causes for metabolic acidosis (MA) in sick children. The biochemical disturbance usually responds to appropriate oxygenation and fluid management, as well as treatment of the underlying cause such as sepsis. It is important to bear in mind other causes of acidosis if improvement does not follow routine correction of the metabolic disturbance. In order to further evaluate a MA, the anion gap needs to be calculated. This reveals whether the acidosis is due to changes in bicarbonate or chloride or whether other anions are responsible for the disturbance. The anion gap is calculated as
Eur J Pediatr
follows: [Na+ +K+]−[HCO3− +Cl−]. A normal anion gap is 10–18 mmol/l. It is generally accepted that conditions with a normal anion gap are due to bicarbonate loss, for example, renal tubular acidosis or excess gut losses. When the anion gap is raised, an additional anion must be present. This is commonly in the form of lactate or ketones, acetoacetate and 3-hydroxy-n-butyrate. Recognised causes of a raised anion gap include sepsis, diabetic ketoacidosis, ingestion of methanol or ethylene glycol and chronic renal failure [2]. Less commonly, organic acids arising from inborn errors of metabolism can be responsible. When a high anion gap MA cannot be accounted for by exclusion of common factors, other causes should be sought. Here, we present the case of raised anion gap MA resulting from transient 5-oxoprolinuria.
Case A 15-month-old girl, from non-consanguineous parents, presented to the emergency department with an 11-day history of diarrhoea (15–20 times daily) and vomiting (after every feed). Paracetamol (60 mg/kg/day) had been given for the preceding 10 days. Both parents had had gastroenteritis, but her four siblings were all in good health. On examination, she had Kussmaul breathing, tachycardia (190 bpm), poor peripheral perfusion, was unresponsive and hypoglycaemic (2.1 mmol/l). She was given 2 ml/kg of 10 % dextrose and received a 20 ml/kg bolus of 0.9 % saline. Her initial gas showed a profound MA (pH 7.0, pCO2 2.4 kPa, base excess −25.8, HCO3− 6.5 mmol/l, anion gap 31.9 mmol/ l). Her chest x-ray showed opacification throughout the left side for which intravenous cefotaxime was commenced. Despite further fluid resuscitation, her acidaemia worsened (pH 6.87, pCO 2 4.13 kPa, base excess −26.2, HCO 3 − 5.0 mmol/l, anion gap 33.4 mmol/l) and she required intubation and ventilation. Multiple inotropes were required (dobutamine 5 mcg/kg/min, noradrenaline 0.8 mcg/kg/min and vasopressin 0.06 units/kg/min) as well as high ventilation pressures and a chest drain to evacuate the empyema. Her initial infection markers were markedly elevated with a white cell count of 62.7×109/l (ref. 5–14), neutrophils 56.3 109/l (ref. 1.5–7.5) and a CRP of 63 mg/l (ref. 0–10). The child continued to have a severe MA despite resuscitation with 70 ml/kg of 0.9 % saline, 10 mg/kg human albumin solution, a half correction of 8.4 % sodium bicarbonate, a packed red cell transfusion (initial Hb 9.2 g/l (ref. 11–13.3)) and boluses of fresh frozen plasma (PT 39.3 s (ref. 10.6–14.9), APTT 67.3 s (ref. 24–35.6)). Regardless of these interventions, the anion gap remained markedly elevated at 30 mmol/l and the moderately raised lactate of 4.9 mmol/l (ref.
CASE REPORT
Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant Sarah L. Hulley 1 & Jeff Perring 1 & Nigel Manning 1 & Simon Olpin 1 & Sufin Yap 1
Received: 22 April 2015 / Revised: 15 June 2015 / Accepted: 18 June 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Transient 5-oxoprolinuria is a phenomenon that is well recognised in adults. We illustrate an unusual paediatric case of transient 5-oxoprolinuria presenting during an episode of severe sepsis with concomitant paracetamol use. The 15month-old patient had an extremely high anion gap metabolic acidosis. Adequate resuscitation failed to correct the biochemical disturbance, and high levels of 5-oxoproline were identified. A combination of haemofiltration, replenishment of glutathione stores with N-acetylcysteine and cessation of paracetamol administration resulted in the resolution of the acidosis. Subsequent testing following treatment of the sepsis revealed no ongoing 5-oxoprolinuria. Conclusion: Transient 5-oxoprolinuria has been previously reported in the adult population during episodes of severe sepsis and various pharmaceutical interventions. This case illustrates that it is a phenomenon that should be considered in paediatric patients where a very high anion gap metabolic acidosis exists that cannot be explained by the biochemical indices.
What is Known: • 5-oxoprolinuria in the paediatric population is usually secondary to an inborn error of metabolism. • Transient 5-oxoprolinuria is well recognised in adults during episodes of severe glutathione depletion. What is New: • Transient 5-oxoprolinuria is a phenomenon rarely reported in the paediatric population. • It highlights the importance of investigating a high anion gap such that unusual diagnoses are not missed.
Keywords Anion gap . Metabolic acidosis . 5-oxoproline . Paracetamol . Pyroglutamate
Abbreviations CRP C-reactive protein MA Metabolic acidosis NAPQI N-acetylbenzoquinoneimine
Communicated by Beat Steinmann * Sufin Yap [email protected] Sarah L. Hulley [email protected] Jeff Perring [email protected] Nigel Manning [email protected] Simon Olpin [email protected] 1
Sheffield Children’s NHS Foundation Trust, Sheffield Children’s Hospital, Western Bank, Sheffield S10 2TH, UK
Introduction Hypovolaemia and hypoxia are relatively common causes for metabolic acidosis (MA) in sick children. The biochemical disturbance usually responds to appropriate oxygenation and fluid management, as well as treatment of the underlying cause such as sepsis. It is important to bear in mind other causes of acidosis if improvement does not follow routine correction of the metabolic disturbance. In order to further evaluate a MA, the anion gap needs to be calculated. This reveals whether the acidosis is due to changes in bicarbonate or chloride or whether other anions are responsible for the disturbance. The anion gap is calculated as
Eur J Pediatr
follows: [Na+ +K+]−[HCO3− +Cl−]. A normal anion gap is 10–18 mmol/l. It is generally accepted that conditions with a normal anion gap are due to bicarbonate loss, for example, renal tubular acidosis or excess gut losses. When the anion gap is raised, an additional anion must be present. This is commonly in the form of lactate or ketones, acetoacetate and 3-hydroxy-n-butyrate. Recognised causes of a raised anion gap include sepsis, diabetic ketoacidosis, ingestion of methanol or ethylene glycol and chronic renal failure [2]. Less commonly, organic acids arising from inborn errors of metabolism can be responsible. When a high anion gap MA cannot be accounted for by exclusion of common factors, other causes should be sought. Here, we present the case of raised anion gap MA resulting from transient 5-oxoprolinuria.
Case A 15-month-old girl, from non-consanguineous parents, presented to the emergency department with an 11-day history of diarrhoea (15–20 times daily) and vomiting (after every feed). Paracetamol (60 mg/kg/day) had been given for the preceding 10 days. Both parents had had gastroenteritis, but her four siblings were all in good health. On examination, she had Kussmaul breathing, tachycardia (190 bpm), poor peripheral perfusion, was unresponsive and hypoglycaemic (2.1 mmol/l). She was given 2 ml/kg of 10 % dextrose and received a 20 ml/kg bolus of 0.9 % saline. Her initial gas showed a profound MA (pH 7.0, pCO2 2.4 kPa, base excess −25.8, HCO3− 6.5 mmol/l, anion gap 31.9 mmol/ l). Her chest x-ray showed opacification throughout the left side for which intravenous cefotaxime was commenced. Despite further fluid resuscitation, her acidaemia worsened (pH 6.87, pCO 2 4.13 kPa, base excess −26.2, HCO 3 − 5.0 mmol/l, anion gap 33.4 mmol/l) and she required intubation and ventilation. Multiple inotropes were required (dobutamine 5 mcg/kg/min, noradrenaline 0.8 mcg/kg/min and vasopressin 0.06 units/kg/min) as well as high ventilation pressures and a chest drain to evacuate the empyema. Her initial infection markers were markedly elevated with a white cell count of 62.7×109/l (ref. 5–14), neutrophils 56.3 109/l (ref. 1.5–7.5) and a CRP of 63 mg/l (ref. 0–10). The child continued to have a severe MA despite resuscitation with 70 ml/kg of 0.9 % saline, 10 mg/kg human albumin solution, a half correction of 8.4 % sodium bicarbonate, a packed red cell transfusion (initial Hb 9.2 g/l (ref. 11–13.3)) and boluses of fresh frozen plasma (PT 39.3 s (ref. 10.6–14.9), APTT 67.3 s (ref. 24–35.6)). Regardless of these interventions, the anion gap remained markedly elevated at 30 mmol/l and the moderately raised lactate of 4.9 mmol/l (ref.
