尿素循环障碍所致新生儿高氨血症基因筛查和早期干预

Genetic screening and early intervention in neonatal hyperammonemia caused by urea cycle disorder

目的探讨广东地区新生儿尿素循环障碍(UCD)的发病率,以实现UCD相关新生儿高氨血症(NHA)早期识别与干预。方法收集2019年至2022年广东地区多中心38159个新生儿基因筛查数据,统计UCD新生儿基因阳性率,分析基因筛查中确诊的9例与UCD相关NHA患儿临床干预和疗效。结果UCD基因阳性率0.472%,Citrin缺陷病最常见(基因阳性率0.314%)。其中3例Citrin缺陷病均为SLC 25A13基因c.852_855delTATG纯合致病性变异,不同的确诊和临床干预时期,预后不同。另外6例UCD相关NHA患儿起病早,病情进展快,经积极早期对症治疗后,2例瓜氨酸血症I型患儿好转,4例患儿死亡和1例失访。结论NHA的病因复杂多样,以UCD最为常见,临床表现缺乏特异性,容易漏诊、误诊,早期血、尿代谢筛查联合UCD相关基因筛查可实现UCD相关NHA的早期识别和诊疗,可指导遗传咨询和再次妊娠的产前诊断。

Objective To explore the prevalence of neonatal urea circulation disorder(UCD)by genetic screening and achieve the early identification and intervention of neonatal hyperammonemia(NHA)caused by UCD in Guangdong province.Methods The gene screening data of 38159 neonates from multiple centers in Guangdong region from 2019 to 2022 were collected,and the gene positive rate of UCD neonates was calculated.Meanwhile,the clinical intervention and efficacy of 9 children with UCD related NHA were further analyzed.Results The gene positive rate of UCD in newborns in Guangdong was 0.472%,and citrin deficiency was the commonest(0.314%).All three cases of citrin deficiency had homozygous variation of c.852_855delTATG in SLC 25A13 gene.Due to the different diagnosis time and clinical intervention period,the prognosis of children is also different.Six children with UCD related NHA had early onset and advanced progression.After active early symptomatic treatment,two patients with citrullinemia typeⅠimproved,four patients died and one was lost to followup.Conclusions The etiology of NHA is complex and diverse,and UCD is the commonest.Its clinical manifestations lack specificity,and it is easy to be missed and misdiagnosed.Early blood and urine metabolism screening combined with UCD-related gene screening can achieve early identification,diagnosis and treatment of UCD-related NHA,and can guide genetic counseling and prenatal diagnosis of another pregnancy.