[Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants].

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.目的： 分析CAD基因变异致尿苷反应性发育性癫痫性脑病（DEE）50型患儿的临床特点。 方法： 以2018至2022年首都医科大学附属北京儿童医院和北京大学第一医院儿科收集的6例CAD基因变异致尿苷反应性DEE50型患儿为研究对象进行回顾性分析。对患儿的病例资料包括癫痫发作、贫血、外周血涂片情况，头颅磁共振成像（MRI）、视觉诱发电位（VEP）结果，基因型特点及尿苷治疗效果等进行描述性分析。 结果： 6例患儿中男3例、女3例，年龄为3.5（3.2，5.8）岁，均表现为难治性癫痫、红细胞生成障碍性贫血和智力及运动发育落后伴倒退。癫痫发作起病年龄为8.5（7.5，11.0）月龄，发作形式以局灶性发作最常见（6例）。6例患儿贫血程度轻至重度不等，4例患儿应用尿苷治疗前行外周血涂片检查提示红细胞形态异常，大小不等，并且可见破碎红细胞，在尿苷治疗6（2，8）个月后复查外周血涂片均恢复正常。2例患儿于2岁时诊断斜视。3例患儿眼底检查正常而VEP提示可疑视神经受累，其中2例分别于尿苷治疗1和3个月复查VEP，显示明显好转和正常。5例患儿头颅MRI提示大脑及小脑皮质萎缩样改变，应用尿苷治疗1.1（1.0，1.8）年后复查均提示明显好转。所有患儿应用尿苷100 mg/（kg·d）口服起始治疗，起始治疗年龄为1.0（0.8，2.5）岁，治疗时间为2.4（2.2，3.0）年。6例患儿应用尿苷治疗后数天至1周内均癫痫发作控制或明显减少。4例患儿仅尿苷单药治疗，癫痫无发作时间分别为7个月、2.4年、2.4年和3.0年。其中1例患儿应用尿苷治疗后癫痫无发作3.0年，已停用尿苷1.5年。2例患儿尿苷合并1~2种抗癫痫发作药物治疗，癫痫发作频率1~3次/年，癫痫无发作8个月和1.4年。 结论： CAD基因变异致尿苷反应性DEE50型主要表现为难治性癫痫、红细胞生成障碍性贫血和智力、运动发育落后伴倒退三联征，还可能存在视神经受累，早期诊断和应用尿苷干预可显著改善临床症状。.