Citrin缺乏所致新生儿肝内胆汁淤积症预后分析

Prognostic analysis of neonatal intrahepatic cholestasis caused by citrin deficiency

目的探讨Citrin缺乏所致新生儿肝内胆汁淤积症(NICCD)患儿临床和实验室检查特征、突变基因及预后。方法以2017年1月至2019年12月成都市妇女儿童中心医院经基因确诊为Citrin缺乏所致新生儿肝内胆汁淤积症患儿6例为研究对象。收集其临床及实验室检测数据,并进行随访。结果 6例患儿平均出生体质量为2.95 kg,均于婴儿期起病。4例以皮肤黄染退而复现就诊,1例以生长迟缓就诊,1例以腹胀就诊。实验室检查结果提示6例患儿AST、γ-谷氨酰转肽酶、碱性磷酸酶、总胆红素、直接胆红素、总胆汁酸均升高,3例患儿ALT升高,2例伴血乳酸升高以及3例甲胎蛋白升高,1例白蛋白降低、2例活化部分凝血活酶时间延长。基因分析提示SLC25A13基因突变,包括:c.852-855del、c.615+5G>A、c.1177+1G>A、IVS16ins3kb、c.1362C>G、1210G>T c.1660-c.1661insGAGATTACAGGTGGCTGCCCGGG。就诊后予以无乳糖、强化中链甘油三酯配方奶喂养,其中5例平均治疗24 d症状明显缓解,1岁以内肝功能完全恢复正常,病例6就诊时已出现肝硬化、腹水、肝功能衰竭,伴发感染,最终放弃治疗。平均随访年龄1岁9月,均有喜高蛋白高脂饮食偏好。结论胆汁淤积性肝病患儿原因分析时应考虑到NICCD,早期就诊,早期行基因分析有助于早期确诊,确诊后给予饮食干预,治疗效果好,预后可,但仍需长期随访。

Objective To investigate the clinical and laboratory features,gene mutations and prognosis of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods Six NICCD patients diagnosed by gene detection from January 2017 to December 2019 in our department were enrolled.Clinical data of these patients were collected and analyzed.Results The average birth weight of the 6 patients was 2.95 kg,and all of them experienced disease onset in infant period.The chief complaints were repeated jaundice(4/6),growth retardation(1/6)and abdominal distension(1/6).Laboratory data showed that all the 6 patients had increased aspartate aminotransferase,γ-glutamyl transferase,alkaline phosphatase,total bilirubin,direct bilirubin and total bile acid.Most had increased alanine aminotransferase(3/6),increased lactic acid(2/2),increased alphafetoprotein(3/3),decreased albumin(1/6)and prolonged activated partial thromboplastin time(2/4).Mutations were found in SLC25 A13 gene,which included c.852-855 del,c.615+5 G>A,c.1177+1 G>A,IVS16 ins3 kb,c.1362 C>G,1210 G>T,and c.1660-c.1661 insGAGATTACAGGTGGCTGCCCGGG.After feeding with lactose-free and medium-chain triglyceride-rich formula,liver function improved 24 days later and normalized completely within 1 year in5 of the infants.Another case had cirrhosis,ascites and liver failure,accompanied by infection at first visit and finally gave up treatment.The average follow-up age was 1 year and 9 months.All of them had the preference for a high protein and high fat diet.Conclusion NICCD should be taken into account in the etiology of infant cholestasis.Early visit and early genetic testing are helpful in early diagnosis.Most Children with NICCD have good prognosis after diet intervention,and long-term follow-up is required.