Faculty Collaboration Database

Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med 2007 May 31;356(22):2282-92

Date

06/01/2007

Pubmed ID

17538087

DOI

10.1056/NEJMoa066596

Scopus ID

2-s2.0-34249803312 (requires institutional sign-in at Scopus site)   303 Citations

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 micromol per liter (1804 microg 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.

Author List

Enns GM, Berry SA, Berry GT, Rhead WJ, Brusilow SW, Hamosh A

Author

William Rhead MD, PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Age Factors
Age of Onset
Amino Acid Metabolism, Inborn Errors
Ammonia
Carbamoyl-Phosphate Synthase I Deficiency Disease
Child
Child, Preschool
Citrullinemia
Female
Humans
Hyperammonemia
Infant
Infant, Newborn
Male
Ornithine Carbamoyltransferase Deficiency Disease
Phenylacetates
Sodium Benzoate
Survival Analysis
Urea