Citrin缺陷致新生儿肝内胆汁淤积症40例临床分析

摘要/Abstract

摘要： 目的分析Citrin缺陷导致的新生儿肝内胆汁淤积症(NICCD)的临床特征、SLC25A13基因突变类型及早期预后,以提高儿科医生对该病的诊治水平。方法回顾性分析40例NICCD患儿的临床特征、基因结果及治疗转归,并进一步分析不同喂养方式下肝功能指标恢复情况有无差异。结果 NICCD患儿出生体重偏低(2.92±1.01)kg,以黄疸为首诊原因,伴圆胖脸(31/40,77.50%)、肝大(25/40,62.50％)、脾大(10/40,25.00％)及生长发育迟缓(13/40,32.50%)。AST、直接胆红素、γ-谷氨酰转肽酶均100%升高,同时伴有高乳酸(37/40,92.50%)、低蛋白血症(36/40,90.00%)、低血糖(26/40,65.00%)、贫血(18/40,45.00%)等改变,可伴血串联质谱及尿气相色谱质谱有机酸分析异常。SLC25A13基因分析发现8种突变类型,最常见的类型为Ⅰ型(37/40,92.50%)、Ⅲ型(10/40,25.00%)、Ⅹ型(9/40,22.50%)突变,纯合突变以Ⅰ型纯合突变为主(19/20,95.00%)。经改变喂养方式等治疗,患儿病情逐渐缓解,主要肝功能指标于治疗1个月时54.80%(17/31)的患儿恢复正常,治疗1年时97.50%(39/40)患儿恢复正常。进一步分析发现,治疗2周时,无乳糖并强化MCT配方奶粉喂养组肝功能指标恢复情况优于单纯无乳糖配方奶粉喂养组。结论 NICCD主要临床表现为黄疸、肝脾肿大、肝功能异常、生长发育迟缓等;常见的SLC25A13基因突变类型为Ⅰ型、Ⅲ型和Ⅹ型。

关键词: Citrin蛋白缺陷, 肝内胆汁淤积症, 临床特征, 预后

Abstract: Objective To analyze the main clinical manifestations, laboratory features and prognosis of neonatal intrahepatic cholestasis caused by Citrin deficiency (NICCD).Methods The clinical characteristics, genetic results and therapeutic outcomes of 40 children with NICCD were retrospectively analyzed, and the differences in the recovery of liver function indicators under different feeding modes were further analyzed.Results Children with NICCD had low birth weight (2.92±1.01) kg, with jaundice as the primary cause, accompanied by chubby face (31/40 cases, 77.50%), large liver (25/40 cases, 62.50%), large spleen (10/40 cases, 25.00%), and growth retardation (13/40 cases, 32.50%). Glutamate transaminase, direct bilirubin and γ-glutamyl transferase were all 100% increased, accompanied by changes of high lactic acid (37/40 cases, 92.50%), hypoproteinemia (36/40 cases, 90.00%), hypoglycemia (26/40 cases, 65.00%), anemia (18/40 cases, 45.00%), and abnormal organic acid analysis by blood tandem mass spectrometry and urinalysis gas chromatography-mass spectrometry. SLC25A13 gene analysis found that 8 types of mutations, The most common types were type I (37 / 40 cases, 92.50%), type III (10 / 40 cases, 25.00%), type X (9 / 40 cases, 22.50%), and homozygous mutations were mainly type I homozygous mutations (19 / 20 cases, 95.00%). After the change of feeding mode and other treatment, the disease of the children gradually alleviated, and the main liver function indicators of the children returned to normal in 1 month of treatment 54.80% (17/31 cases), and in 1 year of treatment 97.50% (39/40 cases). Further analysis showed that the recovery of liver function indexes in the lactose free and MCT fortified formula feeding group was better than that in the lactose free formula feeding group after 2 weeks of treatment.Conclusion For children with cholestasis who conform to the main clinical manifestations of NICCD, genetic testing and early diagnosis should be improved as soon as possible, and treatment such as lactose free and intensive MCT formula feeding should be given. The change of feeding pattern is crucial to the recovery of the disease.

Key words: Citrin deficiency, Intrahepatic cholestasis, Clinical characteristics, Prognosis

房春晓, 陈敏霞, 杨峰霞, 谭丽梅, 叶家卫, 徐翼. Citrin缺陷致新生儿肝内胆汁淤积症40例临床分析[J]. 肝脏, 2021, 26(1): 71-74.

FANG Chun-xiao, CHEN Min-xia, YANG Feng-xia, TAN Li-mei, YE Jia-wei, XU Yi. Clinical analysis of neonatal intrahepatic cholestasis caused by Citrin deficiency:report of 40 cases[J]. Chinese Hepatolgy, 2021, 26(1): 71-74.

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