Clinical analysis of neonatal intrahepatic cholestasis caused by Citrin deficiency:report of 40 cases

Abstract

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

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.

References

[1] 费强,俞惠民. Citrin缺陷导致的新生儿肝内胆汁淤积症诊治进展.中华新生儿科杂志, 2018,33:234-237.
[2] 宋元宗.儿科遗传性胆汁淤积症诊断与治疗新进展.中华实用儿科临床杂志, 2017,32:561-565.
[3] 孙梅.婴儿胆汁淤积症//王卫平,孙锟,常立文.儿科学.北京:人民卫生出版社, 2018:234-237.
[4] 肖长雪,李中跃. Citrin缺陷致新生儿肝内胆汁淤积症29例临床分析及疗效随访.中华实用儿科临床杂志, 2016, 31:518-521.
[5] 刘圣垣,黄志华,董琛.婴儿胆汁淤积1106例临床分析.中国实用儿科杂志, 2013, 28:585-589.
[6] 卢春婷,李佳萦,冯烈,等. Citrin缺陷导致的新生儿肝内胆汁淤积症患SLC25A13基因突变与生化指标的相关性研究.中国病理生理杂志, 2014, 30:859-863.
[7] 罗玲英,杨丽,刘俐,等.SLC25A13基因突变在Citrin缺陷新生儿肝内胆汁淤积症生化指标变化中的临床意义.临床和实验医学杂志, 2019, 18:2081-2084.
[8] Chen HW, Chen HL, Ni YH, et al. Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency. J Pediatr Gastmenteml Nutr, 2008,47: 187-192.
[9] Lu CT, Shi QP, Li ZJ, et al. Blood glueose and insulin and correlation of SLC25A13 mutations with biochemical changes in NICCD patients. Exp BM Med (Maywood), 2017, 242:1535370217710918.
[10] 张领领,鄢素琪,周俪珊,等.Citrin缺陷导致新生儿肝内胆汁淤积症的临床特征及中药利胆合剂治疗效果观察.中国中西医结合急救杂志, 2017,24: 133-136.
[11] 邢雅智,邱文娟,叶军,等. Citrin缺陷导致的新生儿肝内胆汁淤积症临床和SLC25A13基因突变的研究.中华医学遗传学杂志, 2010,27:180-185.
[12] Stapleton C, Boulter E, Balasubramaniam S. Citrin deficiency:a rare but important metabolic disorder to consider in infants with faltering growth and hyperbilirubinaemia. J Pediatr Child Health,2017,53:1229-1232.
[13] 程静,刘丽,李秀珍. NICCD患儿尿半乳糖醇水平GC/MS分析的比较.中国妇幼保健, 2008, 23:4851-4853.
[14] 姜涛,姚蔚,欧阳文献,等. Citrin缺陷所致婴儿肝内胆汁淤积症43例分析.临床肝胆病杂志, 2014,30:1123-1126.

[1]	ZHANG Da-li, ZHOU Xia, FENG Dan-ni, HE Xi, WANG Hong-bo, GAO Yin-jie, SUN Yan-ling, ZHANG Li-juan, LIU Zhen-wen, LIU Hong-ling. Prognosis analysis of liver transplantation for patients with hepatocellular carcinoma using different criteria [J]. Chinese Hepatolgy, 2020, 25(9): 915-918.
[2]	YAN Hua, ZHENG Li-min, YANG Xiao-hong. Influence of intrahepatic cholestasis on liver stiffness measurement value [J]. Chinese Hepatolgy, 2020, 25(9): 943-945.
[3]	WANG Fei, HU Jing, WANG Yi-ming. The analysis of clinical characteristics of transfusion and non transfusion chronic hepatitis C virus infection [J]. Chinese Hepatolgy, 2020, 25(9): 946-947.
[4]	WANG Tao, LI Mu-song, HAN Qiu-ran, LI Cai-hong, SUN Jing-wei. Analysis of the incidence and prognosis of spontaneous portosystemic shunt in patients with cirrhosis [J]. Chinese Hepatolgy, 2020, 25(9): 948-951.
[5]	LI Jing, XIONG Li-jing, DU Li-na, JIANG Mao-lin, YANG Jing, XIE Xiao-li. Prognostic analysis of neonatal intrahepatic cholestasis caused by citrin deficiency [J]. Chinese Hepatolgy, 2020, 25(9): 961-964.
[6]	ZHANG Yan-wei, YANG Rui, YUE Xin, HAN Guo-rong, WANG Gen-ju. Effects of intrahepatic cholestasis of pregnancy on liver function, inflammatory cytokines and fetal outcome [J]. Chinese Hepatolgy, 2020, 25(9): 982-985.
[7]	ZHANG Hai-ye, PENG Yi, LU Yue-jiu, HE Li-feng. Value of preoperative serum AFP and NLR levels in predicting prognosis of HCC patients [J]. Chinese Hepatolgy, 2020, 25(8): 825-827.
[8]	PEI Guang-li, XIE Jie, LIU De-rong, XU Jin'e. Relationship between signal transducer and activator of transcription-3 in placenta and perinatal outcome in patients with intrahepatic cholestasis of pregnancy [J]. Chinese Hepatolgy, 2020, 25(8): 870-872.
[9]	YANG Rui-yuan, LIU Li-wei, LUO Juan, LI Ke-xin, TIAN Qiu-ju, WANG Yan, ZHAO Xin-yan, JIA Ji-dong. A comparative study of predictive models for acute liver failure in drug-induced liver injury [J]. Chinese Hepatolgy, 2020, 25(7): 671-675.
[10]	GUO Feng-cai, WU Jian-ming, WEI Zheng. Analysis of influencing factors of poor response on treatment of autoimmune hepatitis [J]. Chinese Hepatolgy, 2020, 25(7): 752-754.
[11]	MA Xiang-ming, HOU Jing-yue, FU Qing-jiang, CAO Li-ying.. The clinical and pathological significance of mitochondrial pyruvate carriers in hepatocellular carcinoma [J]. Chinese Hepatolgy, 2020, 25(6): 573-577.
[12]	LIU Tie-feng, XU Shu-ni, WU Shan-shan. Predictive value of combined detection of serum p62 and LC3-II for short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure [J]. Chinese Hepatolgy, 2020, 25(6): 582-584.
[13]	ZHU Ping, ZHAO Jie, CHENG Xue-lian, Li De-liang, ZHANG Wei-ye. Clinical characteristics and diagnosis of citrin deficiency with intrahepatic cholestasis [J]. Chinese Hepatolgy, 2020, 25(6): 585-587.
[14]	LIU dong, SU Kang-le, ZHANG Cui-jie, ZHAI Ya-ling, LI Fang-hua. Relationship between positive expression of HBAg in renal tubules and prognosis of renal function damage associated with hepatitis B virus [J]. Chinese Hepatolgy, 2020, 25(4): 372-374.
[15]	GAO Peng-bin, ZHENG Huan-wei, ZHAO Xiao-yan, WANG De-hua, QIN Hao, MENG Ming-hui, ZHANG Jian-ji, YAN Shuang-huan. The clinical characteristics and prognosis of patients with HBV-ACLF treated by internal medicine [J]. Chinese Hepatolgy, 2020, 25(4): 375-378.