难治性癫痫患儿先天性代谢异常筛查

Screening of inborn errors of metabolism in children with intractable epilepsy

目的探讨难治性癫痫(IE)患儿不同先天性代谢异常情况,以利早期进行病因及对症治疗。方法 50例诊断为IE的患儿纳入本研究。运用气相色谱-质谱(GC-MS)和串联质谱(MS/MS)技术对IE患儿尿和血标本进行包括氨基酸、有机酸、脂肪酸、糖、核苷酸等代谢异常的筛查,并进行尿常规、肝功能、血生化、脑部影像学及脑干听、视觉诱发电位等检查。结果 50例IE患儿中,24例(48.0%)尿筛查异常,其中全身性发作异常率42.9%(6/14),部分性发作异常率33.3%(4/12),全身性或部分性等多种形式发作异常率33.3%(2/6),而婴儿痉挛症异常率66.7%(12/18),婴儿痉挛症尿筛查异常率高于其他发作类型(P均<0.05)。20例IE患儿(14例尿筛异常,6例尿筛正常)进行了血筛查,9例异常。26例尿和/或血筛查异常IE患儿(包括24例尿筛异常和2例尿筛正常但血筛异常病例)中18例(69.2%)有不同程度的智力运动发育落后或倒退,头颅CT或MRI异常15例(57.7%),脑干诱发电位异常14例(53.9%),血生化、血气分析异常5例(19.2%),肝功能异常4例(15.4%),尿常规酮体阳性(+～++)4例(15.4%),皮肤改变5例(19.2%),异常家族史4例(15.4%)。9例(18.0%)IE患儿尿或血筛查结果呈典型改变,确诊为先天性遗传性代谢病。结论先天性代谢异常为IE常见致病原因,尤以婴儿痉挛症多见,因此对IE患儿应尽早进行先天性代谢异常筛查,以助早期诊断及治疗。

Objective To study the inborn errors of metabolism in children with intractable epilepsy（IE）to favor early etiological treatment and expectant treatment. Methods Fifty children diagnosed as having IE were included in this study. Screening of metabolic abnormalities including amino acids, organic acid, fatty acid, sugars and nucleotides on both urine and blood samples was performed by gas chromatography-mass spectrometry（ GC-MS）and tandem mass spectrometry（MS/MS） respectively, and urine routine, hepatic function, blood biochemistry, image of encephalon and brain stem evoked potential （ vision and audition） were examined. Results Of 50 cases of IE children , 24 （48.0%） had abnormality of urine screening in whom the positive rates were 42.9% （6/14） for generalized seizure,33.3% （4/12） for partial seizure,33.3% （2/6） for multiple types of seizure,66. 7% （ 12/ 18） for infantile spasms; the positive rate of urine screening in infantile spasms was higher than those in other types （ all P 〈 0.05）. The blood screening was performed on 20 cases （ 14 cases were abnormal urine screening, 6 cases were normal urine screening） in whom 9 cases presented abnormality. Of 26 cases having abnormal urine and/or blood screening results （ including 14 cases having abnormal urine screening results and 2 cases having normal urine screening while abnormal blood screening）, 18 （69.2%） presented hypoevolutism or retrogression of intelligence and motor function,15 （57.7%） had abnormal encephalic CT or MRI images, 14 （53.9%） had abnormal brain stem evoked potential ,5 （ 19.2% ） showed abnormality of blood biochemistry and blood gas analysis ,4 （ 15.4% ） showed abnormality of hepatic function,4 （15.4%） had positive urine ketone bodies（ ＋ - ＋ ＋ ） ,5 （19.2%） had change of skin,4 （ 15.4% ） had abnormal family history. Among the 26 cases of having abnormal urine and/or blood screening resuhs,9 cases （ 18.0% ） presented typical changes of urine or blood screening were confirmed as having inherited metabolic disorders. Conclusion Inborn errors of metabolism play an important role in the pathogenesis of IE especially in infantile spasms. Screening of inborn errors of metabolism in children with IE should be performed as earlier as possible to provide a help for early diagnosis and treatment.