【摘要】 目的 探讨茂名地区希特林蛋白缺乏症的发病情况与预后，了解SLC25A13基因突变类型及突变发生频率。方法 选取2022年4月至2025年1月茂名地区出生的88 322名新生儿作为研究对象，利用串联质谱技术进行筛查，对瓜氨酸增高患儿或有可疑希特林蛋白缺乏症临床症状患儿作进一步基因确诊，确诊患儿给予治疗并跟踪随访。结果 88 322名新生儿中，串联质谱技术筛查瓜氨酸阳性53例，初筛阳性召回43例，复查瓜氨酸仍阳性23例。最终临床确诊希特林蛋白缺乏所致新生儿肝内胆汁淤积症（neonatal intrahepatic cholestasis caused by citrin deficiency,NICCD）1例，SLC25A13基因确诊10例，其中1例假阴性。总阳性预测值18.87%(10/53)，茂名地区NICCD患病率为1/8029(11/88 322);10例基因确诊NICCD患儿中共检测到5种突变位点，其中前3位分别为：c.852-855delTATG占65.0%(13/20)、c.615+5G>A占15.0%(3/20)、IVS16ins3kb占10.0%(2/20)。11例患儿中有1例拒绝诊疗，最终因肝衰竭死亡，其余10例经规范诊疗，目前发育良好。结论 茂名地区新生儿希特林蛋白缺乏症患病率远高于其他地区，利用串联质谱技术可快速早期发现希特林蛋白缺乏症患儿，但个别患儿筛查可出现假阴性，联合基因测序技术可提高确诊率，实现对遗传代谢病的精准诊疗。更多还原

【Abstract】 Objective To explore the incidence and prognosis of citrin deficiency in Maoming, and to understand mutation types and frequency of SLC25A13 gene. Methods A total of 88 322 newborns born in Maoming from April 2022 to January 2025 were selected as research subjects. These specimens were screened using tandem mass spectrometry. Newborns with elevated citrulline levels or suspected clinical symptoms of citrin deficiency were recalled immediately for further genetic confirmation, and treated confirmed cases were followed up. Results Among 88 322 newborns, 53 cases were positive for citrulline by tandem mass spectrometry, 43 cases were recalled with positive initial screening, 23 cases were still positive for citrulline after re-examination. Finally, 1 case of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD) was clinically diagnosed, and 10 cases were diagnosed with SLC25A13 gene, of which 1 case was false negative. Therefore, the total positive predictive value was 18.87%(10/53), and the prevalence rate of NICCD in Maoming was 1/8029(11/88 322). A total of 5 mutation sites were detected in 10 neonates with NICCD gene diagnosis, and the top 3 mutation sites in the order of proportion were: c.852-855 delTATG accounted for 65.0%(13/20), c.615+5G>A accounted for 15.0%(3/20), IVS16 ins3 kb accounted for 10.0%(2/20). Among the 11 cases, 1 case refused treatment and died of liver failure, while the remaining 10 cases were developing well after standardized treatment. Conclusion The incidence of neonatal citrin deficiency in Maoming is significantly higher than in other areas. Tandem mass spectrometry enables rapid early detection of citrin deficiency, though false-negative results may occur in individual cases. Combining genetic sequencing can improve diagnostic accuracy, and achieve precise management of inherited metabolic diseases.更多还原