Citrin缺陷所致婴儿肝内胆汁淤积症43例分析

姜涛; 姚蔚; 欧阳文献; 谭艳芳; 李双杰

doi:10.3969/j.issn.1001-5256.2014.11.007

Citrin缺陷所致婴儿肝内胆汁淤积症43例分析

DOI: 10.3969/j.issn.1001-5256.2014.11.007

1. 湖南省儿童医院肝病中心
2. 中山大学附属第五医院肿瘤放疗科

详细信息

中图分类号: R725.7
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出版历程
- 收稿日期: 2014-07-24
- 出版日期: 2014-11-20

Intrahepatic cholestasis caused by citrin deficiency: a clinical analysis of 43 infants

Liver Disease Center, Hunan Children's Hospital

摘要

摘要:
目的分析Citrin缺陷所致婴儿肝内胆汁淤积症（NICCD）患儿的临床特点及预后。方法收集2011年7月至2014年4月在湖南省儿童医院就诊43例NICCD患儿的临床资料,应用血串联质谱分析、尿气相色谱质谱分析和基因检测技术进行确诊,并结合临床表现和实验室检查进行分析。各指标比较采用单样本t检验和配对t检验。结果大部分NICCD患儿黄疸出现早,有圆胖脸、肝大、生长发育迟缓。实验室检查提示所有患者胆红素、总胆汁酸、血乳酸、甲胎蛋白和降钙素原均升高,大部分患儿ALT、GGT和血氨升高,白蛋白和血糖降低,血脂和凝血功能异常,部分患儿有肝纤维化指标异常（20/24）和铜蓝蛋白低下（17/20）。32例患儿腹部B超提示有肝大,血串联质谱分析发现多数患儿甲硫氨酸、瓜氨酸、酪氨酸、苏氨酸及多种酰基肉碱增高,尿气相色谱质谱分析发现20例患儿半乳糖、半乳糖醇升高,10例患儿4-羟基苯乳酸、4-羟基苯丙酮酸升高,6例未见异常。基因检测提示851del4、1638ins23和IVS6+5G>A突变,以851del4为主。经去乳糖、强化中链脂肪酸饮食、护肝、利胆等治疗,大部分患儿治疗2月各项指标恢复正常...
- Citrin缺陷 /
- 胆汁淤积,肝内 /
- 婴儿 /
- 点突变 /
- 串联质谱法 /
- 气相色谱-质谱法
Abstract:
Objective To analyze the clinical characteristics and prognosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in infants. Methods The clinical data of43 infants with NICCD in our hospital from July2011 to April2014 were collected. The diagnosis was confirmed by tandem mass spectrometry (MS- MS) analysis of blood, gas chromatography- mass spectrometry (GC- MS) analysis of urine, and genetic testing, and an analysis was performed with reference to clinical manifestations and laboratory results. Results Most patients with NICCD developed jaundice early, with a round, fat face, hepatomegaly, and growth retardation. Laboratory examinations showed increased bilirubin, total bile acids, blood lactic acid, alpha- fetoprotein, and procalcitonin in all patients, increased alanine aminotransferase, gamma- glutamyl transpeptidase, and blood ammonia, decreased albumin and blood glucose, and dyslipidemia and coagulation disorders in most patients, and abnormal liver fibrosis markers (20 /24) and low ceruloplasmin (17 /20) in some patients. Abdominal ultrasound showed hepatomegaly in 32 patients. MS- MS analysis of blood samples revealed distinctive elevation of methionine, citrulline, tyrosine, threonine, and a variety of acyl carnitine in most patients. GC- MS analysis of urine samples revealed elevated galactose and galactitol in 20 patients, elevated 4- hydroxyphenyllactic acid and 4- hydroxyphenylpyruvic acid in 10 patients, and no abnormalities in 6patients. Genetic testing revealed 851del4, 1638ins23, and IVS6 + 5G > A mutations, especially 851del4 mutation. After being treated by giving lactose- free diet, strengthening medium- chain fatty acid diet, protecting the liver, and relieving cholestasis, most patients had normalized indices 2 months later, 2 cases had liver cirrhosis, and 7 cases died. Conclusion The clinical manifestations of NICCD vary in children. MS- MS analysis of blood, GC- MS analysis of urine, and genetic testing should be performed early in children with clinically suspected NICCD to provide intervention in time.
- Citrin deficiency /
- cholestasis, intrahepatic /
- infant /
- point mutation /
- tandem mass spectrometry /
- gas chromatography-mass spectrometry

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参考文献(16)

[1]KOBAYSHI K, USHIKAI M, SONG YZ, et al.Overview of citrin deficiency:SLC25A13 mutations and the frequency[J].J Appl Clin Pediatr, 2008, 23 (20) :1553-1557.

[2]SONG YZ, LI BX, HAO H, et al.Selective screening for inborn errors of metabolism and secondary methylmalonicaciduria in pregnancy at high risk district of neural tube defects:a human metabolome study by GC-MS in China[J].Clin Biochem, 2008, 41 (7-8) :616-620.

[3]SONG YZ, USHIKAI M, KOBAYASHI K, et al.Citrin deficiency is an important etiology for cholestatic liver disease in children[J].Chin J Pediatr, 2009, 47 (8) :624-627. (in Chinese) 宋元宗, 牛饲美晴, 小林圭子, 等.小儿胆汁淤积性肝病的病因学特征[J].中华儿科杂志, 2009, 47 (8) :624-627.

[4]SONG YZ, HAO H, USHIKAI M, et al.A difficult and complicated case study:neonatal intrahepatic cholestasis caused by citrin deficiency[J].Chin J Contemp Pediatr, 2006, 8 (2) :125-128. (in Chinese) 宋元宗, 郝虎, 牛饲美晴, 等.疑难病研究-Citrin缺陷导致的新生儿肝内胆汁淤积症[J].中国当代儿科杂志, 2006, 8 (2) :125-128.

[5]SAHEKI T, KOBAYASHI K.Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset typeⅡcitrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD) [J].J Hum Genet, 2002, 47 (7) :333-341.

[6]KIMURA A, KAGE M, NAGATA I, et al.Histological findings in the rivers of patients with neonatal intrahepatie cholcstasis caused by citrin deficiency[J].Hepatol Res, 2010, 40 (4) :295-303.

[7]SAHEKI T, KOBAYASHI K, IIJIMA M, et al.Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate—glutamate carrier[J].Hepatol Res, 2005, 33 (2) :181-184.

[8]OHURAT, KOBAYASHI K, TAZAWA Y, et al.Clinical pictures of 75patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) [J].J Inherit Metab Dis, 2007, 30 (2) :139-144.

[9]CHEN HW, CHEN HL, NI YH, et al.Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatie cholestasis caused by citrin deficiency[J].J Pediatr Gastroenterol Nutr, 2008, 47 (2) :187-192.

[10]SONG YZ, LI BX, CHEN FP, et al.Neonatal intrahepatic cholestasis caused by citrin deficiency:clinical and laboratory investigation of 13subjects in mainland of China[J].Dig Liver Dis, 2009, 41 (9) :683-689.

[11]SONG YZ, KEIKO K.Citrin Deficiency[J].J Appl Clin Pediatr, 2008, 23 (20) :1564-1565. (in Chinese) 宋元宗, 小林圭子.Citrin缺陷病[J].实用儿科临床杂志, 2008, 23 (20) :1564-1565.

[12]ZENG J, LIU L, PENG MZ, et al.Acylcarnitine spectrum analysis of the neonatal intrahepatic cholestasis caused by citrin deficiency[J].J Clin Pediatr, 2012, 30 (9) :801-804. (in Chinese) 曾军, 刘丽, 彭敏芝, 等.Citrin蛋白缺陷所致新生儿肝内胆汁淤积症酰基肉碱谱分析[J].临床儿科杂志, 2012, 30 (9) :801-804.

[13]DING J, WEN PQ, YIN LF, et al.Urine screen analysis of 27 cases with neonatal intrahepatic cholestasis caused by citrin defects[J].China Med Herald, 2012, 9 (16) :174-176. (in Chinese) 丁娟, 温鹏强, 尹莉芳, 等.27例citrin缺陷导致的新生儿肝内胆汁淤积症尿筛查分析[J].中国医药报导, 2012, 9 (16) :174-176.

[14]XING YZ, QIU WJ, YE J, et al.Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatie cholestasis caused by citrin deficiency[J].Chin J Med Genet, 2010, 27 (2) :180-185. (in Chinese) 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[J].中华医学遗传学杂志, 2010, 27 (2) :180-185.

[15]WEN PQ, WANG GB, CHEN ZL, et al.SLC25A13 gene analysis in neonates with intrahepatic cholestasis caused by citrin deficiency[J].Chin J Contempor Pediatr, 2011, 13 (4) :303-308. (in Chinese) 温鹏强, 王国兵, 陈占玲, 等.Citrin缺陷导致的新生儿肝内胆汁淤积症SLC25A13基因分析[J].中国当代儿科杂志, 2011, 13 (4) :303-308.

[16]TAMAMORI A, OKANO Y, OZAKI H, et al.Neonatal intrahepatic cholestasis caused by citrin deficiency:Severe hepatic dysfunction in an infant requifing liver transplantation[J].Eur J Pediatr, 2002, 161 (11) :609-613.

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