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Carnitine deficiency during valproic acid treatment
1Department of Pediatrics, Drechtsteden Hospital Jacobus, Zwijndrecht, The Netherlands.
Insights
Prolonged valproic acid treatment can cause carnitine deficiency in children. Supplementing with carnitine is recommended if fatigue occurs, with effective symptom reversal observed within a week.
Area of Science:
- Biochemistry
- Pediatric Neurology
- Clinical Pharmacology
Background:
- Valproic acid (VPA) is a widely used antiepileptic and mood-stabilizing drug.
- Long-term VPA therapy is associated with potential adverse effects, including metabolic disturbances.
- Secondary carnitine deficiency is a known complication of certain drug treatments.
Purpose of the Study:
- To investigate the effect of prolonged valproic acid treatment on carnitine levels in children.
- To assess the incidence of biochemical and clinical carnitine deficiency during VPA therapy.
- To evaluate the efficacy of carnitine supplementation in children with VPA-induced carnitine deficiency.
Main Methods:
- Paired plasma samples were collected from thirteen children before and after 9 months of continuous valproic acid treatment.
- Plasma free and total carnitine levels were measured.
- Clinical symptoms, particularly fatigue, were monitored.
Main Results:
- Mean plasma free carnitine decreased by 40% (p=0.0008) and total carnitine by 20% (p=0.016) after 9 months of VPA treatment.
- The esterified/free carnitine ratio increased significantly (p=0.011).
- Two out of thirteen children developed fatigue, while four others showed only biochemical evidence of carnitine deficiency.
Conclusions:
- Prolonged valproic acid treatment leads to significant secondary carnitine deficiency in children.
- Carnitine supplementation (15 mg/kg) effectively reverses clinical symptoms like fatigue within a week.
- Monitoring carnitine levels and considering supplementation is advised for children on long-term VPA therapy, especially if fatigue is present.
Abstract:
Prolonged valproic acid treatment results in secondary carnitine deficiency. In thirteen children paired samples of plasma were drawn at the onset of, and after 9 months of continuous valproic acid treatment. At onset free plasma carnitine values were age dependent; they increased during childhood (r = 0.59, p = 0.016). After 9 months: 1 - mean plasma free carnitine decreased by 40%, from 32.7 mumol/l to 20.9 (p 0.0008 and 3% overlap; 2 - plasma total carnitine decreased by 20%, from 34.9 mumol/l to 27.1 (p 0.016 and no overlap); and 3 - the esterified/free carnitine ratio increased by 40%, from 0.28 to 0.39 (p 0.011 and no overlap). In two out of thirteen patients clinical symptoms were observed, fatigue, besides the biochemical evidence of carnitine deficiency. In four others only biochemical deficiency was found. If the child complains of fatigue during prolonged valproic acid treatment, it is advised to supplement carnitine. A dose of 15 mg/kg body weight is effective to reverse the clinical symptoms of carnitine deficiency within a week. The dose to prevent deficiency is not yet established.