New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA

Aires, C. C. P.; Cruchten, Arno van; IJlst, Lodewijk; Almeida, Isabel Tavares de; Durán, Marinus; Wanders, Ronald J. A.; Silva, Margarida F. B.

doi:10.1016/j.jhep.2010.11.031

Cited by 89 publications

(69 citation statements)

References 50 publications

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“…It is usually brought on by pregnancy, infectious illnesses or fasting with subsequent catabolism or the use of sodium valproate which unmasks latent CPS-1 or OTC deficiency (Gropman et al, 2007). Sodium valproate is known to cause hyperammonaemia (Aires et al, 2011). Diagnosis is performed by measuring ammonia levels and enzyme activity in leukocytes or cultured fibroblasts.…”

Section: The Role Of the Liver In Ammonia Metabolismmentioning

confidence: 99%

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

Brannelly

Shield

Killard

2016

Critical Reviews in Analytical Chemistry

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Section: The Role Of the Liver In Ammonia Metabolismmentioning

confidence: 99%

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

Brannelly

Shield

Killard

2016

Critical Reviews in Analytical Chemistry

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“…The influence of urease-producing bacteria and renal dysfunction were considered to be the causes of hyperammonemia in this case, but since renal dysfunction alone rarely causes hyperammonemia, the main cause of hyperammonemia was suspected to be infection with urease-producing bacteria. Hyperammonemia may occur due to the side effects of drugs such as valproic acid [10,11], but she was not medicated with any drugs that could cause hyperammonemia.…”

Section: Discussionmentioning

confidence: 99%

A Case of Infectious Enterocolitis with Hyperammonemia

Otsuji

Simizu

Endo

et al. 2017

J UOEH

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: Case reports of hyperammonemia due to urease-producing bacteria are found occasionally, but most of them are associated with urinary tract infections. We experienced a case of infectious enterocolitis with hyperammonemia in which the causative bacteria was speculated to be urease-producing bacteria. A Japanese woman in her 70s had been diagnosed with microscopic polyangiitis in a nearby hospital and was transferred to our hospital. Although the microscopic polyangiitis was relatively under control after treatment with steroids and rituximab, frequent diarrhea with hyperammonemia (324 μg/dl) appeared and she became comatose. Her blood ammonia decreased to 47 µg/dl and her consciousness recovered to a normal state after antibiotic treatment for infectious enterocolitis and ammonia detoxification therapy. Liver dysfunction, portosystemic shunt, excessive protein intake and constipation were not observed, and she took no medications that would cause hyperammonemia. Although culture results could not identify urease-producing bacteria, considering the clinical course, acute hyperammonemia was suspected to be due to urease-producing bacteria infection. It is necessary to consider the influence of urease-producing bacteria as a cause of acute hyperammonemia not only in urinary tract infections but also in infective enterocolitis.

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“…This metabolite depletes the N-acetyl glutamate by inhibition of N-acetyl Glutamate synthetase N-acetyl glutamate is a cofactor for urea cycle rate-limiting enzyme carbamoyl phosphate synthetase (CPS 1) [10] . Depletion of N-acetyl glutamate results in inhibition of CPS 1, the rate-limiting enzyme of the urea cycle.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Valproic Acid-Induced Hyperammonemia with Encephalopathy (VIHE): A Case Report

et al. 2018

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Valproic acid (VPA) is a wide spectrum antiepileptic medication indicated for seizure prophylaxis across the spectrum of epilepsy. Since coming into clinical use, VPA has also been recommended for the management of a variety of other pathologies, including, most notably, mood stabilization in the manic patient.VPA's common adverse effects include gastrointestinal, influenza-like symptoms, headache, and difficulties with sleep; nonetheless, in rare instances, VPA has been noted to cause the severe and potentially lethal condition of hyperammonemia with encephalopathy (VIHE).VIHE is the result of a dose-independent increase in ammonia levels. Often the patient is asymptomatic; if symptoms reach clinical threshold, lethargy is most common, though seizures, focal neurologic deficits and even coma are possible. VIHE can occur in patients despite normal hepatic function, normal loading doses, chronic stable doses and normal free serum drug levels. Once the diagnosis is confirmed, the first approach for symptomatic patients is to discontinue VPA, start alternative mood stabilizer as indicated, and supplement hyperammonemia treatment with lactulose, carnitine or carglumic acid. Below is a case report of VIHE that developed in an adolescent girl with a history of Bipolar I Disorder who was hospitalized in our facility for stabilization of mania. As demonstrated below, early diagnosis of VIHE is pivotal in reducing morbidity and ultimately can be life-saving.

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New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA

Cited by 89 publications

References 50 publications

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

A Case of Infectious Enterocolitis with Hyperammonemia

Valproic Acid-Induced Hyperammonemia with Encephalopathy (VIHE): A Case Report

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