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Hyperamino-acidaemia and hyperammonaemia in epileptic children treated with valproic acid
K Iinuma1, K Hayasaka, K Narisawa
1Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Insights
Valproic acid (VPA) therapy in epileptic children can lead to hyperammonaemia and altered amino acid levels, suggesting potential mitochondrial dysfunction. Monitoring these levels is crucial for patients on VPA treatment.
Area of Science:
- Biochemistry
- Pediatric Neurology
- Clinical Pharmacology
Background:
- Epilepsy is a common neurological disorder in children.
- Valproic acid (VPA) is a widely used antiepileptic drug.
- VPA therapy can be associated with adverse effects, including metabolic disturbances.
Purpose of the Study:
- To investigate the impact of valproic acid (VPA) therapy on serum amino acid patterns and blood ammonia levels in epileptic children.
- To determine the incidence of hyperammonaemia in children treated with VPA.
- To explore potential correlations between VPA, amino acid levels, and hyperammonaemia.
Main Methods:
- Serum amino acid profiles, blood ammonia, and serum valproic acid (VPA) levels were measured in 75 epileptic children.
- Patients were categorized based on VPA therapy (alone or in combination with other antiepileptic drugs) and compared to controls.
- Statistical analysis was performed to identify significant correlations and differences.
Main Results:
- Hyperammonaemia (serum ammonia > 60 mumol/l) was observed in 19% of patients on VPA alone and 20% on VPA with other drugs.
- No hyperammonaemia was noted in children treated with other antiepileptic drugs.
- Elevated serum glycine, alanine, and serine levels were more prevalent in VPA-treated groups, with significant positive correlations among these amino acids.
Conclusions:
- Valproic acid (VPA) therapy in epileptic children is associated with an increased risk of hyperammonaemia.
- VPA treatment may induce alterations in amino acid metabolism, specifically affecting glycine, alanine, and serine.
- The observed biochemical changes suggest a potential VPA-induced mitochondrial dysfunction.
Abstract:
Serum amino acid pattern, blood ammonia, and serum valproic acid (VPA) levels were estimated in 75 epileptic children with and without VPA therapy. The incidence of patients with hyperammonaemia (greater than 60 mumol/l) in patients treated with only VPA or with a combination of VPA and other antiepileptic drugs was 19% and 20% respectively. Hyperammonaemia was not observed in patients receiving other drugs. Elevated levels of serum glycine, alanine and serine were more common in epileptic patients treated with VPA alone and with VPA in combination with other drugs than in patients receiving other drugs. A significant positive correlation was found between the serum levels of glycine and alanine, of glycine and serine, and of serine and alanine. These findings may indicate a mitochondrial dysfunction caused by VPA.