Van Wouwe J P
Department of Pediatrics, Drechtsteden Hospital Jacobus, Zwijndrecht, The Netherlands.
Int J Vitam Nutr Res. 1995;65(3):211-4.
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.
长期使用丙戊酸治疗会导致继发性肉碱缺乏。对13名儿童在开始使用丙戊酸治疗时以及连续治疗9个月后采集配对的血浆样本。开始时，游离血浆肉碱值与年龄相关；在儿童期呈上升趋势（r = 0.59，p = 0.016）。9个月后：1 - 平均血浆游离肉碱下降40%，从32.7μmol/L降至20.9（p < 0.0008且重叠率为3%）；2 - 血浆总肉碱下降20%，从34.9μmol/L降至27.1（p = 0.016且无重叠）；3 - 酯化/游离肉碱比值上升40%，从0.28升至0.39（p = 0.011且无重叠）。13名患者中有2名除了有肉碱缺乏的生化证据外还出现了临床症状，即疲劳。另外4名患者仅发现生化缺乏。如果儿童在长期丙戊酸治疗期间诉说疲劳，建议补充肉碱。15mg/kg体重的剂量可在一周内有效逆转肉碱缺乏的临床症状。预防缺乏的剂量尚未确定。
