OBJECTIVETo explore the major etiological features of cholestatic liver disease (CLD) in children, and to investigate the molecular epidemiological distribution of SLC25A13 mutations in CLD.

METHODA clinical cross-sectional investigation was performed on 63 CLD cases diagnosed from Oct. 2003 to Mar. 2009 in our department, including 36 males and 27 females. Their clinical data were collected, and etiology and prognosis were analyzed and summarized. Thirteen to 17 mutations in SLC25A13 gene were screened by means of procedures established previously by our group. Several SLC25AJ3 mutations were detected by direct sequencing of DNA fragments amplified by genomic DNA-PCR.

RESULTNo specific etiologies were identified in 24 of the 63 cases. Among the 39 cases with identified etiologies, inherited metabolic diseases were on top of the list, including 6 kinds and 27 cases in total, i.e., neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, 21 cases), transient galactosemia, tyrosinemia type I, galactose kinase deficiency, ornithine carbamoyl transferase deficiency and glycogen storage disease type I, followed by acquired causes (7 cases in total), such as total parenteral nutrition associated cholestasis (TPNAC), congenital syphilis and CMV hepatitis; and then biliary tract malformation (5 cases in total), including biliary atresia, Caroli's disease and gallbladder polyp, were the third. Ten of the 55 patients on follow-up have passed away, while the remaining 45 cases were improved or recovered clinically. SLC25A13 gene analysis were performed in 44 CLD subjects and 21 of them from 20 families (with 40 SLC25A13 alleles in total) were found to have mutations, and the seven mutations detected were 851-854del (23/40), IVS6 + 5G > A (6/40), IVS16ins3kb (3/40), 1638-1660dup (2/30), A541D (1/30), R319X (1/30) and G333D (1/30), respectively, and there were other 3 mutations (3/40) still needing identification in the remaining 3 alleles.

CONCLUSIONThe etiologies for CLD in some cases can not be identified. However, inherited metabolic diseases, including NICCD in particular, constitute common causative factors for CLD. Most of the CLD conditions can be improved, even recovered clinically, although some cases presented with poor prognosis. Seven mutations in SLC25A13 gene were detected, among which, 851-854del, IVS6 + 5G > A, IVS16ins3kb and 1638-1660dup were the leading four mutations, respectively.