Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.
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.
Enns
Gregory M
GM
Department of Pediatrics, Division of Medical Genetics, Stanford University, School of Medicine, Lucile Packard Children's Hospital, Stanford, CA 94305-5208, USA. greg.enns@stanford.edu
Berry
Susan A
SA
Berry
Gerard T
GT
Rhead
William J
WJ
Brusilow
Saul W
SW
Hamosh
Ada
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000641:Ammonia / Q000097:blood; D020165:Carbamoyl-Phosphate Synthase I Deficiency Disease / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D020159:Citrullinemia / Q000188:drug therapy; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000188:drug therapy; D010648:Phenylacetates / Q000009:adverse effects / Q000627:therapeutic use*; D020160:Sodium Benzoate / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014508:Urea / Q000378:metabolism*
D010648:Phenylacetates; D000641:Ammonia; D014508:Urea; C025136:phenylacetic acid; D020160:Sodium Benzoate