南京地区21例SLC25A13基因突变所致Citrin蛋白缺陷引发新生儿肝内胆汁淤积症临床分析

郭红梅; 郑毕霞; 李玫

doi:10.3969/j.issn.1001-5256.2014.11.008

南京地区21例SLC25A13基因突变所致Citrin蛋白缺陷引发新生儿肝内胆汁淤积症临床分析

DOI: 10.3969/j.issn.1001-5256.2014.11.008

南京医科大学附属南京儿童医院消化科

基金项目:

南京市医学科技发展基金(YKK11072)；

详细信息

中图分类号: R722.1
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出版历程
- 收稿日期: 2014-03-14
- 出版日期: 2014-11-20

Neonatal intrahepatic cholestasis caused by citrin deficiency due to SLC25A13 gene mutations: a clinical analysis of 21cases in Nanjing, China

The Affiliated Nanjing Children's Hospital of Nanjing Medical University

Research funding:

摘要

摘要:
目的探讨南京地区新生儿特发性胆汁淤积症（INC）中Citrin蛋白缺陷导致的肝内胆汁淤积症（NICCD）的发病率、SLC25A13基因突变及临床特点。方法对2009年9月到2013年8月南京医科大学附属南京儿童医院收治的152例INC患儿进行SLC25A13基因突变分析。对确诊NICCD的患儿根据年龄及性别与INC患儿进行1∶2配对,比较两组之间的生化指标。计量资料组间比较经Bonferroni校正后采用Mann-Whitney U检验。结果 152例INC患儿中经SLC25A13基因突变分析确诊为NICCD21例（21/152,13.82%）,5种突变类型分别为851854del（27/42,64.29%）、IVS6+5 G→A（7/42,16.67%）、1638ins23（5/42,11.90%）、IVS11+1 G→A（2/42,4.76%）、Q259X（1/42,2.38%）。NICCD组ALT、AST、胆汁酸、白蛋白、空腹血糖、血氨、凝血酶原时间分别为（39.42±23.40）U/L、（124.85±92.65）U/L、（142.43±24.34）μmo...
- Citrin缺陷 /
- 胆汁淤积,肝内 /
- 突变 /
- 婴儿,新生
Abstract:
Objective To investigate the incidence of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in neonates with idiopathic neonatal cholestasis (INC) in Nanjing, China, SLC25A13 gene mutations in these neonates, and clinical features. Methods A total of 152 neonates with INC, who were admitted to the Affiliated Nanjing Children's Hospital of Nanjing Medical University from September 2009 to August 2013, underwent gene analysis for detecting SLC25A13 gene mutations. The neonates were divided into NICCD group, who had been diagnosed definitely, and INC group at a ratio of 1∶ 2, considering the age and gender. Several biochemical indices were compared between the two groups. Comparison of continuous data between the two groups was made by Mann- Whitney U test after Bonferroni correction. Results There were 21 confirmed cases of NICCD (21 /152, 13. 82%) among the 152 neonates with INC; five types of SLC25A13 mutations were identified in the 21 neonates with NICCD, including 851_854del (27 /42, 64. 29%) , IVS6 + 5 G→A (7 /42, 16. 67%) , 1638ins23 (5 /42, 11. 90%) , IVS11 + 1 G→A (2 /42, 4. 76%) , and Q259X (1 /42, 2. 38%) . The alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, bile acid concentration, albumin level, fasting blood glucose, blood ammonia, and prothrombin time for the NICCD group were 39. 42 ± 23. 40 U /L, 124. 85 ± 92. 65 U /L, 142. 43 ± 24. 34 μmol /L, 30. 66 ± 2. 70 g /L, 2. 79 ±0. 54 mmol /L, 117. 57 ± 27. 88 μmol /L, and 14. 03 ± 2. 79 s, respectively, versus 136. 02 ± 113. 67 U /L, 226. 12 ± 129. 26 U /L, 80. 47 ±31. 53 μmol /L, 36. 87 ± 4. 96 g /L, 3. 14 ± 0. 45 mmol /L, 76. 43 ± 20. 80 μmol /L, and 11. 40 ± 1. 55 s for the INC group. The NICCD group had significantly lower ALT and AST levels than the INC group ( Z =- 5. 02, P = 0. 000; Z =- 3. 66, P = 0. 000) ; the NICCD group had a significantly higher bile acid concentration than the INC group ( Z =- 5. 58, P = 0. 000) ; the NICCD group had significantly lower albumin level and fasting blood glucose than the INC group ( Z =- 4. 52, P = 0. 000; Z =- 2. 56, P = 0. 010) ; the NICCD group had a significantly higher blood ammonia level than the INC group (Z =- 4. 75, P = 0. 000) ; the NICCD group had a significantly longer prothrombin time than the INC group (Z =- 4. 10, P = 0. 000) . Conclusion Citrin deficiency due to SLC25A13 gene mutations is an important cause of INC in Nanjing. The three most common mutations are 851_854del, IVS6 + 5 G > A, and 1638_1660dup23, which account for 92. 86% of the SLC25A13 gene mutations. More attention should be paid to clinical analysis and detection of SLC25A13 gene mutations to confirm the diagnosis of NICCD.
- Citrin deficiency /
- cholestasis, intrahepatic /
- mutation /
- infant, newborn

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参考文献(13)

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