Biochemical characteristics of neonatal cholestasis induced by citrin deficiency.
Biochemical characteristics of neonatal cholestasis induced by citrin deficiency.
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DOI：
10.3748/wjg.v18.i39.5601
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发表时间：
2012-10
影响因子：
4.3
通讯作者：
Jian-She Wang;Xiao-hong Wang;Yingying Zheng;Haiyan Fu;Rui Chen;Yi Lu;L. Fang;T. Saheki;Keiko Kobayashi
中科院分区：
文献类型：
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作者：
Jian-She Wang;Xiao-hong Wang;Yingying Zheng;Haiyan Fu;Rui Chen;Yi Lu;L. Fang;T. Saheki;Keiko Kobayashi
目的探讨枸橼酸缺乏所致新生儿肝内胆汁淤积症（NICCD）与其他病因所致新生儿肝内胆汁淤积症生化指标的差异。方法：2003年6月至2010年12月期间，6个月以下的患者被转诊接受结合型高胆红素血症的调查，符合本研究的条件。在排除影响肝外胆道系统的疾病后，对所有患者进行了两种最常见的SLC 25 A13突变的筛查;对整个SLC 25 A13基因的编码外显子进行测序，并在选定的病例中进行柠檬酸蛋白的Western印迹。检测到纯合子或复合杂合子SLC 25 A13突变和/或正常citrin蛋白缺失的患者定义为NICCD患者。在进行全面的结合性高胆红素血症检查后无法确定特定病因的病例被定义为特发性新生儿胆汁淤积症（INC）。32例NICCD患者、250例INC患者和39例经胆管造影证实的胆道闭锁（BA）婴儿入组。从医疗档案中提取第一次就诊时的实验室检查值并进行比较。结果与BA和INC患者相比，NICCD患者的总胆汁酸（TBA）水平显著升高[所有指标均以中位数表示（四分位数间距）：NICCD组为178.0（111.2-236.4）μmol/L，BA组为112.0（84.9-153.9）μmol/L，INC组为103.0（70.9-135.3）μmol/L，P = 0.0001]。NICCD患者的直接胆红素显著降低[D-Bil 59.6（43.1-90.9）μmol/L，NICCD为134.0 BA为（115.9-151.2）μmol/L，（63.0-123.6）μmol/L，P = 0.0001];丙氨酸氨基转移酶[ALT 34.0（23.0-55.0）U/L（NICCD）vs 108.0 BA为（62.0-199.0）U/L，（46.0-166.0）U/L，P = 0.0001];天冬氨酸转氨酶[AST 74.0 NICCD中（53.5-150.0）U/L与153.0 BA为115.0-239.0 U/L，INC（81.0-223.0）U/L，P = 0.0006];白蛋白[34.9（30.7-38.2）g/L，NICCD为38.4（36.3-42.2）g/L;（37.0-42.3）g/L，P = 0.0001];葡萄糖[3.2（2.0-4.4）mmol/L，NICCD vs 4.1（3.4-5.1）mmol/L的BA和4.0 INC中为（3.4-4.6）mmol/L，P = 0.0014]和总胆固醇[TCH 3.33（2.97-4.00）mmol/L，BA为4.57（3.81-5.26）mmol/L，INC为4.00（3.24-4.74）mmol/L，P = 0.0155]。NICCD患者的D-Bil与总胆红素（T-Bil）比值[所有指标均表示为中位数（四分位数间距）：0.54（0.40-0.74）]显著低于BA患者[0.77（0.72-0.81），P = 0.001]和INC患者[0.74（0.59-0.80），P = 0.0045]。NICCD患者的AST/ALT比值[2.46（1.95-3.63）]远高于BA患者[1.38（0.94-1.97），P = 0.0001]和INC患者[1.48（1.10-2.26），P = 0.0001]。NICCD患者的TBA/D-Bil比值显著较高[3.36（1.98-4.43）vs 0.85 BA组为0.72-1.09，INC患者为0.92-1.14，P = 0.0001]，TBA/TCH比值为60.7（32.4-70.9）vs BA患者24.7（19.8-30.2）和INC患者24.2（21.4-26.9），P = 0.0001]与BA和INC组相比。结论NICCD与BA、INC的生化指标有显著性差异。TBA排泄在NICCD似乎更严重的干扰比胆红素和胆固醇。
AIM To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS Patients under 6 mo of age who were referred for investigation of conjugated hyperbilirubinaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homozygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a comprehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range): 178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose [3.2 (2.0-4.4) mmol/L in NICCD vs 4.1 (3.4-5.1) mmol/L in BA and 4.0 (3.4-4.6) mmol/L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol/L in NICCD vs 4.57 (3.81-5.26) mmol/L in BA and 4.00 (3.24-4.74) mmol/L in INC, P = 0.0155] levels. The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range): 0.54 (0.40-0.74)] than that in BA patients [0.77 (0.72-0.81), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045]. A much higher AST/ALT ratio was found in NICCD patients [2.46 (1.95-3.63)] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA/D-Bil ratio [3.36 (1.98-4.43) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA/TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) in BA patients and 24.2 (21.4-26.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION NICCD has significantly different biochemical indices from BA or INC. TBA excretion in NICCD appeared to be more severely disturbed than that of bilirubin and cholesterol.