Hamed Sherifa A, Abdella Mostafa M
Department of Neurology, Assiut University Hospital, Assiut, Egypt.
Epilepsy Res. 2009 Sep;86(1):32-41. doi: 10.1016/j.eplepsyres.2009.04.002. Epub 2009 May 14.
Valproate (VPA) administration may be associated with adverse metabolic effects, among is hyperammonemia, which could suggest metabolic abnormalities as carnitine deficiency. This study aimed to evaluate the risk frequency of hyperammonemia and abnormal carnitine levels in children receiving VPA who were otherwise free of neurological or obvious nutritional problems.
Ammonia levels were prospectively evaluated in 60 epileptic children with primary epilepsy free of neurological or nutritional problems and were treated with VPA for at least 1 year. Forty healthy children were included as controls. Ammonia levels were correlated with total carnitine (TC), free carnitine (FC), acylcarnitine (AC) and AC/FC ratio. The abnormal ammonia and carnitine levels were also re-checked after 3 months treatment with L-carnitine.
Compared to pre-treatment and control levels, the mean TC and FC were lower (p<0.001) while ammonia (p<0.01), AC (p<0.05) and AC/FC ratio (p<0.01) were higher. In the treated group of epileptics, TC and FC were negatively associated with ammonia (r=-0.896, p<0.0001; r=-0.935, p<0.0001). Significant associations were found between FC and AC/FC levels and patient's age (FC; r=0.457, p<0.05, AC/FC; r=-0.435, p<0.05) and dose of VPA (FC; r=-0.753, p<0.001, AC/FC; r=0.591, p<0.01). Ammonia was correlated with patients' age (r=-0.532, p<0.01) and dose of VPA (r=0.673, p<0.01). The abnormal ammonia and carnitine levels were returned to normal after L-carnitine supplementation.
Epileptic children treated with VPA and free of neurological disabilities are at risk for hyperammonemia that may be associated with hypocarnitinemia. Patients will benefit from early recognition and preventive measures as carnitine supplementation.
丙戊酸盐（VPA）治疗可能与不良代谢效应相关，其中包括高氨血症，这可能提示存在如肉碱缺乏等代谢异常。本研究旨在评估在无神经或明显营养问题的接受VPA治疗的儿童中高氨血症及肉碱水平异常的风险频率。
对60例无神经或营养问题的原发性癫痫患儿进行前瞻性氨水平评估，这些患儿接受VPA治疗至少1年。纳入40例健康儿童作为对照。氨水平与总肉碱（TC）、游离肉碱（FC）、酰基肉碱（AC）及AC/FC比值相关。在用左旋肉碱治疗3个月后，再次检查氨及肉碱水平异常情况。
与治疗前及对照水平相比，平均TC和FC较低（p<0.001），而氨（p<0.01）、AC（p<0.05）及AC/FC比值（p<0.01）较高。在接受治疗的癫痫患儿组中，TC和FC与氨呈负相关（r=-0.896，p<0.0001；r=-0.935，p<0.0001）。发现FC和AC/FC水平与患者年龄（FC；r=0.457，p<0.05，AC/FC；r=-0.435，p<0.05）及VPA剂量（FC；r=-0.753，p<0.001，AC/FC；r=0.591，p<0.01）之间存在显著相关性。氨与患者年龄（r=-0.532，p<0.01）及VPA剂量（r=0.673，p<0.01）相关。补充左旋肉碱后，氨及肉碱水平异常恢复正常。
接受VPA治疗且无神经功能障碍的癫痫患儿有发生高氨血症的风险，这可能与低肉碱血症相关。患者将从早期识别及如补充肉碱等预防措施中获益。
