Encefalopatía hiperamoniémica inducida por ácido valproico en un neonato. Tratamiento con ácido carglúmico

Colomer, Belén Fernández; García, S. Rekarte; López, J.E. García; González, Cecilia; Granda, M. Montes; Cotallo, Gil Daniel Coto

doi:10.1016/j.anpedi.2013.09.015

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…VPA has been associated with hyperammonemic encephalopathy, a risk which is obviously increased in patients with urea cycle disorders, with OTC deficiency being the most common. 6,18 It is therefore recommended to determine blood ammonia levels and liver function before starting treatment with VPA. VPA is generally considered safe, but can cause side effects like weight gain, dyspepsia, peripheral edema, fatigue, dizziness, drowsiness, hair loss, headaches, nausea, sedation, and tremors.…”

Section: Discussionmentioning

confidence: 99%

“…3,19,20 In addition, hyperammonemia is a frequent idiosyncratic side effect of VPA therapy that is mostly mild and asymptomatic in children; however, although VHE is rare, it is potentially fatal. 2,6 In pediatric patients, hyperammonemia is defined as blood ammonia levels above 50 μmol/L. 16 Hyperammonemic encephalopathy presents clinically as impaired consciousness (seizure, somnolence, lethargy, confusion, and even stupor and coma).…”

Section: Discussionmentioning

confidence: 99%

“…3 Although VPA-induced hyperammonemic encephalopathy (VHE) is rare (<1/10 000), it is more frequent when VPA is used in combination with other antiepileptic drugs (AEDs) 2,4,5 and it could be a serious condition, that causes a reduction seizure threshold, cerebral edema, and even death. 2,6 VPA is extensively metabolized in the liver, mostly by ß-oxidation in the mitochondria as the main metabolic route (40%), with carnitine being responsible for its entry into the mitochondria, as for all fatty acids. 7 In healthy individuals, upon activation by Nacetylglutamate (NAG), carbamyl phosphate synthetase I (CPSI) catalyzes the reaction of ammonia with carbonate and adenosine triphosphate to form carbamyl phosphate, which is subsequently converted to urea.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of VPA-induced hyperammonemia is not an approved use of CA, even though off-label use for this indication has already been reported, and different clinical practice guidelines suggest that the use of CA in VPA hypermmonemia is available. 6,16,17 The objective of this study was to describe the efficacy of CA in the VPA-induced hyperammonemia in our center.…”

Section: Introductionmentioning

confidence: 99%

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Use of carglumic acid in valproate‐induced hyperammonemia: 25 pediatric cases

et al. 2020

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Hyperammonemic encephalopathy is a rare but potentially dangerous complication of the antiepileptic drug (AED) sodium valproate (VPA). We report a retrospective study of 25 pediatric patients, (15 females [60%]; age: 7.6 ± 4.9 years), with different underlying disorders, who suffered from hyperammonemia due to VPA and who were treated with carglumic acid (CA). The duration of treatment with VPA was 15 ± 1 month, with a dose of 40 ± 16.6 mg/kg/d. VPA blood levels were 75.5 ± 60 mg/L with seven patients being overdosed (>100 mg/L). Twenty‐three patients received concomitant treatment with other AEDs. The initial dose of CA was 100 mg/kg. Subsequently, CA doses of 25 mg/kg were given to 22 patients every 6 hours (average treatment length 2.17 ± 1.1 days) until ammonemia was normalized. In nine patients, CA was used in combination with other drugs to treat hyperammonemia. In all cases, blood ammonia levels were brought under control and symptoms of hyperammonemia resolved. Two hours after CA administration, the average reduction in ammonium levels was 53 ± 29 and 88.6 ± 47.5 μmol/L at 24 hours, resulting in a statistically significant decrease when compared to pretreatment levels. There were no statistically significant differences between sexes, in the presence or not of cognitive impairment or previous carnitine treatment. There were no statistically significant differences when comparing treatment with CA plus ammonia scavengers vs CA alone. In 17 patients (68%) VPA was discontinued and 62% of the patients who maintained treatment had recurrent episodes of hyperammonemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of carglumic acid in valproate‐induced hyperammonemia: 25 pediatric cases

et al. 2020

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“…N-carbamylglutamate (NCG), also known as carglumic acid, which is a synthetic analogue of N-acetylglutamate (NAG), is one of the cofactors essential to the proper functioning of urea cycle [57]. NCG is indicated for treatment of hyperammonemia secondary to NAG-synthetase deficiency [58].…”

Section: Clinical Features and Clinical Managementmentioning

confidence: 99%

Hyperammonemic encephalopathy without hepatic dysfunction due to treatment with valproate: four cases and a mini review

Dinçer

Akgün

Bodur

et al. 2018

Psychiatry and Clinical Psychopharmacology

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Divalproex sodium/valproic acid (VPA) is an antiepileptic drug which is frequently prescribed in neurology and psychiatric clinics. Common side effects of VPA are side effects of the digestive system, weight gain, tremor, sedation, hematologic side effects and hair loss. Valproate-induced hyperammonemia is almost seen in 50% of patients treated with VPA, some of which may develop encephalopathy. Valproate-induced hyperammonemic encephalopathy (NE) is a well-known subject and there are numerous publications in the current literature. Although there is substantial evidence for this side effect in patients with neurological disorders, the data in the psychiatric area are limited. When we look at publications, it seems that VHE is seen more often because it starts earlier in psychiatric patients, but we think that it is often missed. Here, we presented five cases in which we followed up and treated with VHE diagnosis in our clinic within one year and other reports published previously in a table.

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Valproate

2015

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S Valproate Hyperammonaemic encephalopathy: case reportA 20-day-old boy developed hyperammonaemic encephalopathy while receiving valproate.The boy was admitted for a skull fracture and subdural haematoma secondary to occipital trauma. His partial seizures were successfully treated with phenobarbital and midazolam; however, he subsequently experienced a new episode of prolonged secondarily generalised partial seizure. He received an initial bolus of valproate at 15 mg/kg, and then maintenance regimen at 1 mg/kg/h. Forty eight hours after the initiation of valproate therapy, he was noted to have decreased level of consciousness and spontaneous movement with significant hypotonia and hyporeflexia. An EEG revealed generalised lowvoltage slow activity compatible with cerebral oedema. A gasometry revealed respiratory alkalosis. His valproate levels were slightly elevated, and his serum ammonia level was found to be 398 µmol/L.Valproate therapy was discontinued, and the boy was treated with carglumic acid and carnitine. Five hours later, phenylbutyrate and L-arginine were added. At 10 hours, his ammonia level dropped to 182 µmol/L and the valproate level returned within the normal range. At 18 hours, the ammonia level returned to normal and his condition improved. He was monitored on an outpatient basis and evolved favourably. Author comment: "We describe the case of a 20-day-old male, who developed a serious VHE after receiving [valproate] for refractory neonatal seizures." Fernandez Colomer B, et al. Valproate-induced hyperammonemic encephalopathy in a neonate: Treatment with carglumic acid. Anales de Pediatria

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Encefalopatía hiperamoniémica inducida por ácido valproico en un neonato. Tratamiento con ácido carglúmico

Cited by 5 publications

References 16 publications

Use of carglumic acid in valproate‐induced hyperammonemia: 25 pediatric cases

Use of carglumic acid in valproate‐induced hyperammonemia: 25 pediatric cases

Hyperammonemic encephalopathy without hepatic dysfunction due to treatment with valproate: four cases and a mini review

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