HOME HELP CONTACT US SUBSCRIPTIONS CME ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Take the CME quiz: Vol. 7 No. 9, September 2006 E-Letters: Submit a response Alert me when this article is cited Alert me when E-Letters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Niemi, A.-K. Articles by Enns, G. M. Search for Related Content PubMed Articles by Niemi, A.-K. Articles by Enns, G. M.

NeoReviews Vol.7 No.9 2006 e486
© 2006 American Academy of Pediatrics

Pharmacology Review: Sodium Phenylacetate and Sodium Benzoate in the Treatment of Neonatal Hyperammonemia

^* Department of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Stanford, Calif

Abbreviations: AL: argininosuccinic acid lyase • ASA: argininosuccinic acid • ATP: adenosine triphosphate • BZ: benzoate • CoA: coenzyme A • HIP: hippurate • NABZ: sodium benzoate • NAPA: sodium phenylacetate • OTC: ornithine transcarbamylase • PA: phenylacetic acid • PAGN: phenylacetylglutamine • PD: peritoneal dialysis • UCD: urea cycle disorder

The first 300 words of the full text of this article appear below.

	Introduction

 
Ammonia is present in all body fluids and exists primarily as ammonium ion at physiologic pH. Hyperammonemia is defined as a blood ammonia concentration greater than about 100 mcmol/L in neonates or 50 mcmol/L in children and adults (precise cut-offs vary, depending on individual laboratory normative ranges). The concentration of ammonia is 10 times higher in tissue than in blood. A 5- to 10-fold increase in blood ammonia concentration usually is toxic to the nervous system.

Hyperammonemia in the neonatal period, especially when due to inborn errors of metabolism, can progress rapidly and cause severe neurologic damage or early death. Hyperammonemia can be caused by inborn errors of metabolism as well as by a variety of acquired conditions (Tables 1 and 2). Urgent treatment is required because of the potential for irreversible neurologic sequelae that can, in many cases, be prevented by prompt diagnosis and institution of therapy.

Table 1. Inborn Errors of Metabolism Associated With Hyperammonemia

Urea cycle defects N-acetylglutamate synthetase deficiency Carbamyl phosphate synthetase deficiency Ornithine transcarbamylase deficiency Argininosuccinate synthetase deficiency (citrullinemia) Argininosuccinate lyase deficiency Arginase deficiency Amino acid transporter deficiencies Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome Lysinuric protein intolerance Citrin deficiency (citrullinemia type II) Organic acidemias Methylmalonic acidemia Propionic acidemia Isovaleric acidemia Multiple carboxylase deficiency Multiple acyl-CoA dehydrogenase deficiency 3-Hydroxymethylglutaryl-CoA dehydrogenase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Oxothiolase deficiency L-2-Hydroxyglutaric acidemia 3-Methylglutaconyl-CoA hydratase deficiency Fatty acid oxidation defects Carnitine transporter deficiency Carnitine palmitoyl transferase 2 deficiency Carnitine-acylcarnitine translocase deficiency Medium-chain acyl-CoA dehydrogenase deficiency Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency Very-long-chain acyl-CoA dehydrogenase deficiency Pyruvate carboxylase deficiency Mitochondrial disorders Hyperinsulinism/hyperammonemia syndrome (glutamate dehydrogenase mutations) Delta1-pyrroline-5-carboxylate synthase deficiency

Table 2. Causes of Acquired Hyperammonemia

Sampling artifact Cardiovascular Patent ductus venosus Portocaval shunt Hypovolemia Congestive heart failure Perinatal asphyxia Liver failure Infectious hepatitis (eg, herpes simplex virus) Bacterial colonization (urease-positive organisms) Neurogenic bladder Prune belly syndrome Blind loop syndrome Ureterosigmoidostomy Iatrogenic Valproate Arginine deficiency Total parenteral nutrition

The combination of sodium phenylacetate (NAPA) and sodium benzoate (NABZ) in a 10%/10% solution is an intravenously administered United States Food and Drug Administration (FDA)-approved drug used as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients who have urea cycle disorders (UCDs). Its concomitant use with protein restriction, provision of adequate calories to prevent catabolism, arginine hydrochloride, and hemodialysis in treating neonatal hyperammonemia helps prevent the reaccumulation of ammonia by increasing waste nitrogen excretion. The purpose of this article is to review the pharmacology and use of NAPA/NABZ in the treatment of neonatal hyperammonemia.

	Neonatal Hyperammonemia

 
Because the inheritance of most inborn errors of metabolism that cause neonatal hyperammonemia is autosomal recessive (exceptions include ornithine transcarbamylase [OTC] deficiency, which is X-linked, and hyperinsulinism/hyperammonemia syndrome, which is autosomal dominant), family history may offer no information of note or . . . [Full Text of this Article]