摘要目的 分析戊二酸尿症1型患者的临床、生化和基因突变特点.方法 总结北京大学第一医院儿科2003年7月-2013年10月确诊并随访的28例戊二酸尿症1型患者的临床特点、代谢筛查结果、头颅磁共振成像特点以及GCDH基因分析结果,并结合文献复习.结果 (1)28例患者中3例经新生儿筛查发现,余25例为发病后于2个月～17岁获诊.(2)通过新生儿筛查发现者(3例)无明显临床症状.早发型22例(79％)为婴儿期起病,临床主要表现为智力、运动落后或倒退(21例)、肌张力障碍(20例)、惊厥发作(5例)、手足徐动(2例)、呕吐(2例)、嗜睡(1例)和喂养困难(1例).20例遗留不同程度的智力、运动落后,仅2例发育正常.晚发型3例(11％),8 ～16岁发病,临床主要表现为运动倒退(2例)、阵发性头痛(2例)和惊厥发作(1例),治疗后恢复良好,智力及运动恢复如常.(3)23例接受了头颅核磁共振检查,22例有异常表现:特征性的外侧裂增宽、基底节损害、脑白质异常和脑萎缩.(4)28例共检出了35种不同的GCDH基因突变,c.148T＞ C(p.W50R)最常见,发生率为7.7％.未报道的新突变6种(c.628A＞G、c.700C＞T、c.731G＞T、c.963G＞C、c.1031C＞T和c.l109T＞C).结论 戊二酸尿症1型常导致智力、运动障碍、肌张力异常等严重神经系统损害,患者临床表型多样,发病年龄越早症状越重,预后大多不良.患者的临床表型、生化表型与基因型无明显相关性.新生儿筛查是早期发现患者的关键.

abstractsObjective To investigate the clinical,biochemical and genetic profiles of 28 Chinese patients with glutaric aciduria type 1.Method Twenty-eight patients with glutaric aciduria type 1 seen in the Department of Pediatrics,Peking University First Hospital from July 2003 to October 2013 were studied.The data of clinical course,laboratory examinations,cranial MRI and GCDH gene mutations of the patients were analyzed.Result (1) Three cases were detected by newborn screening,and the other patients were diagnosed at the age of 2 months to 17 years.(2) 22 patients (79％) were infant onset cases with psychomotor retardation,dystonia,seizures,athetosis,recurrent vomiting,drowsiness or feeding difficulty.Only two of the 22 patients with infant onset got normal intelligence and movement after treatment.Twenty of them were improved slowly with delayed development,dystonia and other neurological problems.Three patients (11％) had late onset.They had motor regression,headache and seizure at the age of 8,9 and 17 years,respectively.Rapid improvement was observed after treatment.(3) Cranial MRI has been checked in 23 patients ; 22 of them showed characteristic widening of the Sylvian fissure,abnormalities of the basal ganglia,leukoencephalopathy and brain atrophy.Thirty-five mutations in GCDH gene of the patients were identified; c.148T ＞ C (p.W50R)was the most common mutation with the frequency of 7.7％ ; 6 mutations (c.628A ＞ G,c.700C ＞T,c.731G ＞ T,c.963G ＞ C,c.1031C ＞ T and c.1109T ＞ C) were novel.Conclusion Glutaric aciduria type 1 usually induced neurological deterioration resulting in severe psychomotor retardation and dystonia.Most of our patients were clinically diagnosed.Patients with early onset usually remained having neurological damage.Phenotype and genotype correlation has not been found in the patients.Neonatal screening for organic acidurias should be expanded in China.