Palomino Pérez Laura María, Martín-Rivada Álvaro, Cañedo Villaroya Elvira, García-Peñas Juan José, Cuervas-Mons Vendrell Margarita, Pedrón-Giner Consuelo
Section of Gastroenterology and Nutrition Hospital Infantil Universitario Niño Jesús Madrid Spain.
Section of Pediatrics Hospital Infantil Universitario Niño Jesús Madrid Spain.
JIMD Rep. 2020 Jun 11;55(1):3-11. doi: 10.1002/jmd2.12131. eCollection 2020 Sep.
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.
高氨血症性脑病是抗癫痫药物（AED）丙戊酸钠（VPA）一种罕见但潜在危险的并发症。我们报告一项对25例儿科患者（15例女性[60%]；年龄：7.6±4.9岁）的回顾性研究，这些患者患有不同的基础疾病，因VPA导致高氨血症，并接受了卡谷氨酸（CA）治疗。VPA治疗持续时间为15±1个月，剂量为40±16.6mg/kg/d。VPA血药浓度为75.5±60mg/L，7例患者用药过量（>100mg/L）。23例患者同时接受了其他AED治疗。CA初始剂量为100mg/kg。随后，22例患者每6小时给予25mg/kg的CA（平均治疗时长2.17±1.1天），直至血氨水平恢复正常。9例患者中，CA与其他药物联合用于治疗高氨血症。所有病例中，血氨水平均得到控制，高氨血症症状消失。CA给药2小时后，血铵水平平均降低53±29μmol/L，24小时时降低88.6±47.5μmol/L，与治疗前水平相比有统计学显著下降。在性别、是否存在认知障碍或既往肉碱治疗情况方面，均无统计学显著差异。比较CA加氨清除剂与单独使用CA的治疗效果，也无统计学显著差异。17例患者（68%）停用了VPA，维持治疗的患者中有62%出现高氨血症复发。
