浙江省新生儿鸟氨酸氨甲酰转移酶缺乏症筛查及随访分析  

Newborn screening for ornithine transcarbamylase deficiency in Zhejiang Province and the follow-up analysis

作　　者：周朵[1] 杨茹莱[1] 黄新文[1] 童凡[1] 黄晓磊[1] 钱古柃[1] 杨昕[1] 杨建滨[1] 赵正言[1] Zhou Duo;Yang Rulai;Huang Xinwen;Tong Fan;Huang Xiaolei;Qian Guling;Yang Xin;Yang Jianbin;Zhao Zhengyan(Department of Genetics and Metabolism,Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,National Children′s Regional Medical Center,Hangzhou 310052,China)

机构地区：[1]浙江大学医学院附属儿童医院遗传与代谢科,国家儿童健康与疾病临床医学研究中心,国家儿童区域医疗中心,杭州310052

出　　处：《中华实用儿科临床杂志》2023年第1期43-48,共6页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的了解浙江省新生儿鸟氨酸氨甲酰转移酶缺乏症(OTCD)的患病率、临床特征及转归情况。方法采用回顾性研究,应用串联质谱技术对2009年1月至2021年12月浙江大学医学院附属儿童医院遗传与代谢科4261036名新生儿进行遗传代谢病筛查,结合尿有机酸分析及OTC基因检测确诊。确诊患儿进行饮食和生活管理,补充瓜氨酸、精氨酸治疗,长期进行随访观察并评估患儿的生长和智能发育情况。结果确诊OTCD 7例,均为男性,2例为新生儿期发病型,5例为迟发型,患病率为1.6/100万。除1例无异常临床表现外,余6例均数次发病,伴高氨血症及肝功能损害,其中1例新生儿期发病死亡。患儿新生儿筛查血瓜氨酸不同程度降低,4例尿嘧啶升高,其中1例合并乳清酸升高。7例患儿携带OTC基因半合子突变,6例为错义突变(c.604C>T、c.386G>A、c.779T>C、c.1019C>T、c.594C>G、c.931G>A),1例为内含子突变(c.514-35C>G),其中c.594C>G、c.514-35C>G为新发变异。结论浙江新生儿筛查OTCD患病率低,为1.6/100万,均为男性,新生儿筛查均存在低瓜氨酸血症。OTCD临床表现高度异质,新生儿期OTCD发病较为严重,存活者常遗留严重后遗症,迟发型多数出现高氨血症及肝功能损害。基因型与临床表现型可能存在一定相关性,发现2种新发变异,拓展了OTCD的基因谱。Objective To investigate the incidence,clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD)in newborns in Zhejiang Province.Methods A retrospective research was conducted.A total of 4261036 newborns from Department of Genetics and Metabolism,Children′s Hospital,Zhejiang University School of Medicine,between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management,and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated.Results A total of 7 patients with OCTD were diagnosed,with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD,and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients,inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients,and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene,including 6 missense variations(c.604C>T,c.386G>A,c.779T>C,c.1019C>T,c.594C>G,c.931G>A)and 1 intron variation(c.514-35C>G).Two variants(c.594C>G,c.514-35C>G)were never reported previously.Conclusions The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified,which further expands the mutational spectrum.

关 键 词：鸟氨酸氨甲酰转移酶缺乏症 尿素循环障碍 新生儿筛查 

分 类 号：R722.1[医药卫生—儿科]