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Orphanet J Rare Dis. 2016 Sep 23;11(1):127.

Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

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Etablissement Pharmaceutique des Hôpitaux de Paris, AGEPS, 7 rue du Fer à Moulin, Paris, 75005, France.
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Robert-Debré, AP-HP, Paris, France.
Reference Centre for Inherited Metabolic Disorders, Hôpital Femme Mère-Enfant, Lyon, France.
Centre de Référence des Maladies Héréditaires du Métabolisme, CHU Timone Enfants, Marseille, France.
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Jeanne-de-Flandre, CHRU Lille, Lille, France.
Reference Centre for Inherited Metabolic Disorders (MaMEA), Hôpital Necker-Enfants Malades, Institut Imagine, Université Paris Descartes, 149 rue de Sèvres, 75743, Paris, Cedex 15, France.
Centre de Référence des Maladies Héréditaires du Métabolisme, CHU de Nancy, Hôpital Brabois Enfants, Vandoeuvre-les-Nancy, France.
URC/CIC Paris Centre, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France.



The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases.


Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another treatment for hyperammonemia (sodium phenylacetate + sodium benzoate, haemofiltration). Eighteen side effects were reported related to the i.v. infusion (local diffusion, oedema).


This 10-year retrospective study shows that i.v. sodium benzoate associated with an emergency regimen is an effective and safe treatment for acute episodes of UCD.


Clinical trials; Hyperammonemia; Sodium benzoate; Systematic review; Urea cycle disorders

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