Abstract：Objective To explore the clinical characteristics and genetic findings of patients with infantile intrahepatic cholestasis. Methods The clinical data were collected in children who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from June 2017 to June 2019 and were suspected of inherited metabolic diseases. Next generation sequencing based on target gene panel was used for gene analysis in these children. Sanger sequencing technology was used to verify the genes of the members in this family. Results Forty patients were enrolled. Pathogenic gene variants were identified in 13 patients (32%), including SLC25A13 gene variation in 3 patients who were diagnosed with citrin deficiency, JAG1 gene variation in 3 patients who were diagnosed with Alagille syndrome, ABCB11 gene variation in 3 patients who were diagnosed with progressive familial intrahepatic cholestasis type 2, HSD3B7 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, AKR1D1 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, NPC1 gene variation in 1 patient who was diagnosed with Niemann-Pick disease, and CFTR gene variation in 1 patient who was diagnosed with cystic fibrosis. Conclusions The etiology of infantile intrahepatic cholestasis is complex. Next generation sequencing is helpful in the diagnosis of infantile intrahepatic cholestasis.
WANG Mei-Juan,ZHONG Xue-Mei,MA Xin et al. Clinical characteristics and gene variants of patients with infantile intrahepatic cholestasis[J]. CJCP, 2021, 23(1): 91-97.
Fischler B, Lamireau T. Cholestasis in the newborn and infant[J]. Clin Res Hepatol Gastroenterol, 2014, 38(3):263-267.
[2]
Togawa T, Sugiura T, Ito K, et al. Molecular genetic dissection and neonatal/infantile intrahepatic cholestasis using targeted next-generation sequencing[J]. J Pediatr, 2016, 171:171-177.e4.
[3]
Nicastro E, Di Giorgio A, Marchetti D, et al. Diagnostic yield of an algorithm for neonatal and infantile cholestasis integrating next-generation sequencing[J]. J Pediatr, 2019, 211:54-62.e4.
[4]
Lipiński P, Ciara E, Jurkiewicz D, et al. Targeted next-generation sequencing in diagnostic approach to monogenic cholestatic liver disorders-single-center experience[J]. Front Pediatr, 2020, 8:414.
[5]
Moyer V, Freese DK, Whitington PF, et al. Guideline for the evaluation of cholestatic jaundice in infants:recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2004, 39(2):115-128.
[6]
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
[7]
Okano Y, Ohura T, Sakamoto O, et al. Current treatment for citrin deficiency during NICCD and adaptation/compensation stages:strategy to prevent CTLN2[J]. Mol Genet Metab, 2019, 127(3):175-183.
[8]
Lipiński P, Jurkiewicz D, Ciara E, et al. Neonatal cholestasis due to citrin deficiency:diagnostic pitfalls[J]. Acta Biochim Pol, 2020, 67(2):225-228.
[9]
Dimmock D, Maranda B, Dionisi-Vici C, et al. Citrin deficiency, a perplexing global disorder[J]. Mol Genet Metab, 2009, 96(1):44-49.
[10]
Abuduxikuer K, Chen R, Wang ZL, et al. Risk factors associated with mortality in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and clinical implications[J]. BMC Pediatr, 2019, 19(1):18.
[11]
Zhang ZH, Lin WX, Zheng QQ, et al. Molecular diagnosis of citrin deficiency in an infant with intrahepatic cholestasis:identification of a 21.7kb gross deletion that completely silences the transcriptional and translational expression of the affected SLC25A13 allele[J]. Oncotarget, 2017, 8(50):87182-87193.
[12]
Kamath BM, Baker A, Houwen R, et al. Systematic review:the epidemiology, natural history, and burden of alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2018, 67(2):148-156.
[13]
Guegan K, Stals K, Day M, et al. JAG1 mutations are found in approximately one third of patients presenting with only one or two clinical features of Alagille syndrome[J]. Clin Genet, 2012, 82(1):33-40.
Shah I, Chilkar S. Progressive familial intrahepatic cholestasis type 2 in an Indian child[J]. J Pediatr Genet, 2017, 6(2):126-127.
[18]
Wang HH, Wen FQ, Dai DL, et al. Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid:a case report and review of the literature[J]. World J Gastroenterol, 2018, 24(35):4086-4092.
[19]
Kamal N, Surana P, Koh C. Liver disease in patients with cystic fibrosis[J]. Curr Opin Gastroenterol, 2018, 34(3):146-151.
[20]
Eminoglu TF, Polat E, Gökçe S, et al. Cystic fibrosis presenting with neonatal cholestasis simulating biliary atresia in a patient with a novel mutation[J]. Indian J Pediatr, 2013, 80(6):502-504.
