Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 21, 2012; 18(39): 5601-5607
Published online Oct 21, 2012. doi: 10.3748/wjg.v18.i39.5601
Biochemical characteristics of neonatal cholestasis induced by citrin deficiency
Jian-She Wang, Xiao-Hong Wang, Ying-Jie Zheng, Hai-Yan Fu, Rui Chen, Yi Lu, Ling-Juan Fang, Takeyori Saheki, Keiko Kobayashi
Jian-She Wang, Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai 200540, China
Jian-She Wang, Xiao-Hong Wang, Hai-Yan Fu, Rui Chen, Yi Lu, Ling-Juan Fang, The Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
Ying-Jie Zheng, Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China
Takeyori Saheki, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan
Keiko Kobayashi, Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
Author contributions: Wang JS, Wang XH, Zheng YJ and Fu HY contributed equally to this paper; Wang JS proposed the idea and wrote the first draft of this paper; Zheng YJ contributed to the statistical analysis and created all the figures; Fu HY contributed to the data collection; Wang JS, Fu HY, Chen R, Saheki T and Kobayashi K contributed to the gene tests and Western blotting; Wang JS, Wang XH and Lu Y contributed to patient management; and all the authors contributed to the design, data analysis, draft revision and final approval of the paper for publishing.
Supported by National Science Foundation of China, No. 30973230 and No. 81070281
Correspondence to: Jian-She Wang, Professor, Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai 200540, China. jshwang@shmu.edu.cn
Telephone: +86-21-64931171 Fax: +86-21-64931171
Received: April 12, 2012
Revised: June 27, 2012
Accepted: July 9, 2012
Published online: October 21, 2012
Abstract

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.

Keywords: Cholestasis; Biliary atresia; Infants; Idiopathic neonatal cholestasis; SLC25A13