鸟氨酸氨甲酰基转移酶缺乏症临床特点并文献分析

Clinical characteristics of ornithine carbamoyltransferase deficiency and literature review

目的探讨1例迟发型鸟氨酸氨甲酰基转移酶缺乏症(OTCD)患儿的临床特点,并结合相关文献进行分析。方法选择2015年9月13日,因"间歇性呕吐7d,抽搐1d"于南京市儿童医院重症监护病房救治的1例10月龄OTCD男性患儿为研究对象。采用回顾性方法,分析其临床病历资料,主要包括新生儿期串联质谱(MS/MS)检测结果、临床表现、实验室检查及治疗情况。检索万方、中国知网及PubMed数据库中关于OTCD的相关文献,并进行分析,总结OTCD的临床特点。结果 (1)病史采集结果:本例患儿出生72h常规进行MS/MS检测的结果显示,瓜氨酸正常;10月龄时,其临床表现为呕吐、嗜睡及抽搐,血氨>200μmol/L,MS/MS检测结果为正常,尿气相色谱质谱(GC/MS)检测结果提示大量乳清酸和尿嘧啶,应用Ion Torrent半导体测序技术,明确其致病位点为鸟氨酸氨甲酰基转移酶(OTC)基因c.386G>A(p.Arg129His),患儿母亲携带c.386G>A(p.Arg129His)突变。对患儿采取低蛋白饮食,精氨酸及苯甲酸钠降血氨等治疗,效果欠佳,并于入院后第20天,家属放弃抢救后死亡。(2)文献检索结果:在本研究检索条件下,共检索到10篇临床资料相对完整的有关OTCD的国内文献,共计纳入12例OTCD患者,以及国外文献5篇,共计纳入5例OTCD患者。其临床特点均显示,OTCD临床表现主要为非特异性消化道和神经系统症状,41.2%(7/17)患者血液样本中瓜氨酸降低,94.1%(16/17)患者尿液样本中乳清酸和尿嘧啶增高,35.3%(6/17)患者进行了OTC基因外显子测序,均发现突变位点,患者病死率高,预后较差。结论 OTCD临床表现缺乏特异性,主要依靠MS/MS、尿GC/MS检测,以及基因检测(OTCD诊断金标准),进行诊断。OTCD患者病死率高,预后差,迄今临床对其尚无标准治疗方案,临床医师需提高对OTCD的认识和诊断、治疗水平。

Objective To explore the clinical characteristics of a late-onset ornithine carbamoyltransferase deficiency （OTCD） child, and analyze OTCD by summarizing pertinent literatures.Methods A 10-month old male child complained with ＂intermittence vomit 7 d, twitched 1 d＂ who was diagnosed as OTCD and rescued in Department of Intensive Care Unit in Nanjing Children′s Hospital on 13 September 2015, was chosen as study subject.The clinical data of the OTCD child was analyzed by retrospective method, including the results of tandem mass spectrometry （MS/MS） detection after born, clinical manifestations, laboratory examination results and therapy.The cases of OTCD were searched from Wanfang, CNKI and PubMed database, and the clinical characteristics of OTCD were summarized.Results ① The case report results were as follows.In this case, routine MS/MS screening was performed in 72 h after birth and the result showed the concentration of citrulline was normal.The child presented with vomiting, lethargy and twitch at the age of 10 months, blood ammonia was over 200 μmol/L, no obvious abnormality was detected of the MS/MS, and his urine gas chromatography-mass spectrometry （GC/MS） revealed a large number of orotic acid and urine uracil.A novel compound mutation of the ornithine carbamoyltransferase （OTC） gene c.386G〉A（p.Arg129His） was identified in the child by Ion Torrent semiconductor sequencing technology.His mother was found of heterozygous with c.386G〉A（p.Arg129His） mutation.Low protein diet was provided for the child and ammonia scavenger treatment were conducted consist of arginine and sodium benzoate.The child died on the 20th day after admission after his family members abandoned treatment for poor treatment effect.② Literature retrieval results were as follows.A total of 10 related domestic literatures of OTCD with relatively complete clinical data were searched and a total of 12 OTCD patients were included, besides, 5 related literatures from abroad of OTCD with relatively complete clinical data were searched and a total of 5 OTCD patients were included.According to the analysis results of literatures, the main clinical manifestations of OTCD were nonspecific digestive tract and nervous system symptoms, 41.2% （7/17） of OTCD patients had decreased concentration of citrulline in their blood sample, and 94.1% （16/17） of OTCD patients had increased concentration of orotic acid and urine uracil in their urine sample.Mutation sites of OTC gene were detected by gene testing in 35.3%（6/17） patients, the mortality rate of OTCD was high, and the prognosis was poor.Conclusions Clinical manifestations of OTCD are not specific, and the diagnosis of OTCD is relied on MS/MS and urine GC/MC detection, and the diagnose golden standard of gene diagnosis.The mortality of OTCD is high and its prognosis is poor.There is no practicable systematic treatment project for OTCD until now, so it is necessary for clinicians to improve the knowledge and the level of diagnosis and treatment of OTCD.