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中华妇幼临床医学杂志(电子版) ›› 2017, Vol. 13 ›› Issue (03) : 287 -292. doi: 10.3877/cma.j.issn.1673-5250.2017.03.008

所属专题: 文献

论著

鸟氨酸氨甲酰基转移酶缺乏症临床特点并文献分析
王彦云1, 孙云1, 蒋涛1,()   
  1. 1. 210004 南京医科大学附属妇产医院 南京市妇幼保健院遗传医学中心
  • 收稿日期:2017-03-10 修回日期:2017-04-25 出版日期:2017-06-01
  • 通信作者: 蒋涛

Clinical characteristics of ornithine carbamoyltransferase deficiency and literature review

Yanyun Wang1, Yun Sun1, Tao Jiang1,()   

  1. 1. Center for Genetic Medicine, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical Univercity/Nanjing Maternity and Child Health Hospital, Nanjing 210004, Jiangsu Province, China
  • Received:2017-03-10 Revised:2017-04-25 Published:2017-06-01
  • Corresponding author: Tao Jiang
  • About author:
    Corresponding author: Jiang Tao, Email:
引用本文:

王彦云, 孙云, 蒋涛. 鸟氨酸氨甲酰基转移酶缺乏症临床特点并文献分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2017, 13(03): 287-292.

Yanyun Wang, Yun Sun, Tao Jiang. Clinical characteristics of ornithine carbamoyltransferase deficiency and literature review[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2017, 13(03): 287-292.

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7 d,抽搐1 d"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72 h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>200 μmol/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.

图1 10月龄OTCD男性患儿及其父母OTC基因外显子测序结果[图1A:患儿OTC基因c.386G>A半合子突变(黄色箭头处);图1B:患儿父亲OTC基因c.386位点检测到正常鸟嘌呤G(黄色箭头处);图1C:患儿母亲OTC基因c.386G>A杂合突变(黄色箭头处)]
表1 2000-2016年国内文献报道的12例OTCD患者临床特点
文献作者 例数 年龄 性别 临床表现 MS/MS检测结果 尿GC/MS检测结果 OTC基因外显子测序结果 预后
卢致琨等[3] 1 2岁 纳差、呕吐 瓜氨酸正常 大量乳清酸,中量尿嘧啶 C.103insA(p.Val35SerfsX7)突变 死亡
金莉蓉等[4] 1 18岁 行为紊乱、间歇性抽搐 瓜氨酸正常 大量乳清酸,尿嘧啶正常 未查 死亡
刘晓景等[5] 1 6个月 纳差、呕吐 前2次结果瓜氨酸正常,第3次为瓜氨酸降低 前2次结果正常,第3次为大量乳清酸和尿嘧啶 IVS1-2A>G突变 病情稳定
周平等[6] 1 7岁 腹痛、呕吐、性格改变 瓜氨酸正常 大量乳清酸和尿嘧啶 未查 病情稳定
王利等[7] 5 生后1 h 早产、全身青紫、呼吸不规则 瓜氨酸正常 大量乳清酸和尿嘧啶 G195R杂合突变 死亡
? ? 2 d 呼吸不规则 瓜氨酸降低 大量乳清酸和尿嘧啶 未查 死亡
? ? 14个月 呕吐、意识障碍 瓜氨酸降低 大量乳清酸和尿嘧啶 未查 病情稳定
? ? 16个月 嗜睡、抽搐 瓜氨酸正常 大量乳清酸和尿嘧啶 未查 病情稳定
? ? 2岁3个月 呕吐、抽搐、精神异常 瓜氨酸正常 大量乳清酸和尿嘧啶 未查 死亡
罗芳等[8] 1 7 d 抽搐 瓜氨酸降低 大量乳清酸,尿嘧啶正常 未查 死亡
汤行录等[9] 1 10个月 运动发育迟缓 瓜氨酸降低 大量乳清酸和尿嘧啶 未查 不详
王颖等[10] 1 10岁 间歇性头痛、意识障碍 瓜氨酸降低 大量乳清酸和尿嘧啶 未查 不详
表2 国外文献报道的5例迟发型OTCD患者临床特点
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