Prenatal benzoate treatment in urea cycle defects

Illsinger, Sabine; Hartmann, Helmut; Oehler, K.; Bohnhorst, Bettina; Kühn‐Velten, W. Nikolaus; Lücke, Thomas

doi:10.1136/adc.2008.144824

Cited by 15 publications

(6 citation statements)

References 5 publications

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“…This strategy is successful in achieving therapeutic levels of benzoic acid in umbilical cord blood as well as in the neonate's serum prior to delivery. SP and SB contain a considerable concentration of Na and chlorine (Cl); thus, it is recommended to avoid the concomitant use of isotonic saline solutions unless in the setting of dehydration [1,76,[83][84][85].…”

Section: Ammonia Scavengersmentioning

confidence: 99%

Hyperammonemia in review: pathophysiology, diagnosis, and treatment

2011

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Ammonia is an important source of nitrogen and is required for amino acid synthesis. It is also necessary for normal acid-base balance. When present in high concentrations, ammonia is toxic. Endogenous ammonia intoxication can occur when there is impaired capacity of the body to excrete nitrogenous waste, as seen with congenital enzymatic deficiencies. A variety of environmental causes and medications may also lead to ammonia toxicity. Hyperammonemia refers to a clinical condition associated with elevated ammonia levels manifested by a variety of symptoms and signs, including significant central nervous system (CNS) abnormalities. Appropriate and timely management requires a solid understanding of the fundamental pathophysiology, differential diagnosis, and treatment approaches available. The following review discusses the etiology, pathogenesis, differential diagnosis, and treatment of hyperammonemia.

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Section: Ammonia Scavengersmentioning

confidence: 99%

Hyperammonemia in review: pathophysiology, diagnosis, and treatment

2011

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“…Even though therapies based on alternative pathways to the urea cycle for nitrogen disposal are usually started soon after birth, prenatal administration might improve metabolic stability. Indeed, prenatal benzoate treatment by benzoate infusion of the mother shortly before birth was proven to be safe and resulted in therapeutic levels of benzoate in umbilical cord blood [105]. Based on this evidence, prenatal infusion of ammonia-scavenging drugs to the mother may reduce postnatal complications due to hyperammonemia and provide a valuable prenatal therapeutic approach in the treatment of UCDs.…”

Section: Expert Opinionmentioning

confidence: 99%

An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

Heras

Aldámiz‐Echevarría

Martínez-Chantar

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas Covered We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert Opinion For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.

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“…If prenatal diagnosis of a urea cycle defect is established, elimination of nitrogen via benzoate can be accelerated by loading the fetus already in utero. We have done this with success in one patient suffering from ornithine transcarbamylase deficiency and another one with citrullinemia by infusing their mothers with benzoate for 24 h before birth (5). This resulted in increased hippurate excretion in the neonates, showing that glycine can be conjugated with benzoate in the liver of newborns.…”

Section: Intoxication Typementioning

confidence: 93%

“…As recently demonstrated by our group, drug therapy of an affected newborn via its mother is possible in urea cycle defects, which may improve outcome (5).…”

Section: Intoxication Typementioning

confidence: 94%

Impact of selected inborn errors of metabolism on prenatal and neonatal development

Illsinger

2010

IUBMB Life

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SummaryIn general, data regarding maturational processes of different metabolic pathways in the very vulnerable fetal and neonatal period are rare. This review is to substantiate the impact of selected inborn errors of metabolism on this critical period of life and their clinical manifestation. Significant adaptation of mitochondrial/energy-, carbohydrate-, lysosomal-, and amino acid-metabolism occurs during early prenatal and neonatal development. In utero, metabolic environment has an impact on the development of the fetus as well as fetal organ maturation.

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Prenatal benzoate treatment in urea cycle defects

Abstract: Benzoate infusion of the mother shortly before birth is safe and results in therapeutic levels of benzoate in umbilical cord blood.

Cited by 15 publications

References 5 publications

Hyperammonemia in review: pathophysiology, diagnosis, and treatment

Hyperammonemia in review: pathophysiology, diagnosis, and treatment

An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

Impact of selected inborn errors of metabolism on prenatal and neonatal development

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