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Previous Volume 356:2282-2292 May 31, 2007 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Shih, V. E. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects.

Methods We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia.

Results Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, P<0.001). Patients 12 or more years of age (93 patients), who had 437 episodes, were more likely than all younger patients to survive (99%, P<0.001). Eighty-one percent of patients who were comatose at admission survived. Patients less than 30 days of age with a peak ammonium level above 1000 µmol per liter (1804 µg per deciliter) were least likely to survive a hyperammonemic episode (38%, P<0.001). Dialysis was also used in 56 neonates during 60% of episodes and in 80 patients 30 days of age or older during 7% of episodes.

Conclusions Prompt recognition of a urea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate.

Source Information

From the Department of Pediatrics, Stanford University, Stanford, CA (G.M.E.); the Department of Pediatrics, University of Minnesota, Minneapolis (S.A.B.); the Department of Pediatrics, Thomas Jefferson University, Philadelphia (G.T.B.); the Department of Pediatrics, Medical College of Wisconsin, Milwaukee (W.J.R.); and the Department of Pediatrics and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore (S.W.B., A.H.).

Address reprint requests to Dr. Enns at the Department of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Lucile Packard Children's Hospital, 300 Pasteur Dr., H-315, Stanford, CA 94305-5208, or at greg.enns{at}stanford.edu.

Full Text of this Article

This article has been cited by other articles:

• Shih, V. E. (2007). Alternative-Pathway Therapy for Hyperammonemia. NEJM 356: 2321-2322 [Full Text]