cblC型甲基丙二酸血症并脑积水的基因特点及疗效分析

Analysis of gene characteristics and therapeutic effect of cblC type methylmalonic acidemia with hydrocephalus

目的分析cblC型甲基丙二酸血症(MMA)并脑积水患儿的临床表现、基因突变类型、治疗效果和预后特点,以提高对该病的认识,为其治疗提供依据。方法选取2015年4月至2019年1月北京大学第一医院小儿外科收治的MMA并脑积水患儿15例,均行基因检测诊断为cblC型MMA。患儿均行侧脑室腹腔分流手术。术后继续药物治疗MMA,以临床表现及头颅影像学检查结果作为调整分流阀依据,适当调整分流阀压力。回顾性分析15例患儿临床资料和基因突变特点,对临床症状、治疗效果、手术并发症及预后进行研究。结果男8例(53.3%),女7例(46.7%);年龄2~33个月;术后随访11~55个月,所有患儿术后随访无死亡,无脑积水术后严重并发症。术前3例(20.0%)头围为正常范围,1例(6.7%)大于正常范围,11例(73.3%)小于正常范围;4例(26.7%)术后转入儿科重症监护室;c.609G>A突变最常见,7例(46.7%)为c.609G>A纯合突变,5例(33.3%)为c.609G>A杂合突变;术后所有患儿颅内高压症状均明显缓解或消失,头围进行性增大停止,前囟张力明显降低,双眼"落日征"消失;视力减退及听力减退较术前均有好转。4例(26.7%)术后智力、运动恢复正常,11例(73.3%)术后遗留轻-重度智力、运动发育障碍;患儿随访期间头颅CT均显示脑室扩张较术前明显缩小,间质性水肿明显改善。结论脑室腹腔分流术治疗cblC型MMA并脑积水效果值得肯定,大部分cblC型MMA并脑积水患儿头围小于正常范围,c.609G>A是cblC型MMA并脑积水患儿的最常见突变,围手术期"代谢危象"可引起严重并发症。

Objective The clinical manifestations,types of gene mutations,therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia(MMA)and hydrocephalus were analyzed to improve the clinical understanding of the disease,so as to provide a basis for the treatment of the disease.Methods From April 2015 to January 2019,15 patients with MMA and hydrocephalus in Department of Pediatric Surgery,Peking University First Hospital were enrolled,and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery,the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed,and the therapeutic effects and prognosis were summarized and analyzed as well.Results There were 8 males(53.3%)and 7 females(46.7%),aged from 2 to 33 months.All the cases were followed up from 11 to 55 months,without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases(20.0%)was in the normal range,1 case(6.7%)was greater than the normal range,and 11 cases(73.3%)were less than the normal range.Four patients(26.7%)were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study,with 7 cases(46.7%)of c.609G>A homozygous mutation,and 5 cases(33.3%)of c.609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased,all"setting-sun"sign of eyes disappeared,and vision loss and hearing loss were better compared with the pre-operation.Four cases(26.7%)displayed normal intelligence and exercise,and 11 cases(73.3%)were left with mild to severe psychomotor retardation.During the follow-up pe-riod,the head CT showed that the ventricle was remarkably narrowed,and interstitial brain edema obviously improved.Conclusions Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative"metabolic crisis"can result in serious complications.