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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 3
Mar.  2022
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Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(3): 613-616

Clinical features of sodium taurocholate cotransporting polypeptide deficiency and an analysis of SLC10A1 gene mutation

DOI: 10.3969/j.issn.1001-5256.2022.03.022

  • Department of Infectious Diseases, Guangzhou Women and Children's Medical Center, Guangzhou 510120, China

Research funding:

Guangzhou Health Science and Technology Project (20201A011036)

More Information
  • Corresponding author: XU Yi, xuyi70@163.com(ORCID: 0000-0001-8971-9334)
  • Received Date: 2021-08-17
  • Accepted Date: 2021-09-20
  • Published Date: 2022-03-20
    Abstract
  •   Objective  To investigate the clinical and gene mutation features of sodium taurocholate cotransporting polypeptide (NTCP) deficiency.  Methods  A total of 10 children, aged < 18 years, who were diagnosed with NTCP deficiency in Guangzhou Women and Children's Medical Center from June 2020 to June 2021 were enrolled, and related data were analyzed, including general information (sex, age, body height, body weight, family history, and past history), clinical manifestation, disease outcome, laboratory examination (routine blood test, liver function, hepatotropic virus, and autoimmune hepatitis screening), and gene mutation.  Results  All 10 children had normal growth and development, among whom there were 8 boys and 2 girls, with an age of 3-37 months at the time of diagnosis. The etiology of children attending the hospital for the first time was prolonged jaundice (5/10, 50%), elevation of aminotransferases (2/10, 20%), abnormal physical examination results (2/10, 20%), and pneumonia (1/10, 10%). At the time of diagnosis, all children had a significant increase in serum total bile acid (TBA), 2 children had increases in alanine aminotransferase and aspartate aminotransferase, and 1 child had an increase in total bilirubin (TBil), mainly direct bilirubin (DBil) (DBil/TBil ratio > 50%). Second-generation gene sequencing showed that all 10 children had a homozygous mutation of the SLC10A1 gene, i.e., c.800C > T(p.Ser267Phe, chr14∶70245193).  Conclusion  Although NTCP deficiency often has no symptoms, some of the children may manifest as infant cholestasis in the early stage. The possibility of NTCP deficiency should be considered when there is persistent hypercholanemia and the changing trend of serum TBA is not consistent with that of other liver function parameters.

     

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    • References(22)
  • [1]
    KARPEN SJ, DAWSON PA. Not all (bile acids) who wander are lost: The first report of a patient with an isolated NTCP defect[J]. Hepatology, 2015, 61(1): 24-27. DOI: 10.1002/hep.27294.
    [2]
    ŠARENAC TM, MIKOV M. Bile acid synthesis: From nature to the chemical modification and synthesis and their applications as drugs and nutrients[J]. Front Pharmacol, 2018, 9: 939. DOI: 10.3389/fphar.2018.00939.
    [3]
    CHIANG J. Bile acid metabolism and signaling in liver disease and therapy[J]. Liver Res, 2017, 1(1): 3-9. DOI: 10.1016/j.livres.2017.05.001.
    [4]
    ANWER MS, STIEGER B. Sodium-dependent bile salt transporters of the SLC10A transporter family: More than solute transporters[J]. Pflugers Arch, 2014, 466(1): 77-89. DOI: 10.1007/s00424-013-1367-0.
    [5]
    APPELMAN MD, CHAKRABORTY A, PROTZER U, et al. N-glycosylation of the Na+-taurocholate cotransporting polypeptide (NTCP) determines its trafficking and stability and is required for hepatitis B virus infection[J]. PLoS One, 2017, 12(1): e0170419. DOI: 10.1371/journal.pone.0170419.
    [6]
    YU Y, LI S, LIANG W. Bona fide receptor for hepatitis B and D viral infections: Mechanism, research models and molecular drug targets[J]. Emerg Microbes Infect, 2018, 7(1): 134. DOI: 10.1038/s41426-018-0137-7.
    [7]
    VAZ FM, PAULUSMA CC, HUIDEKOPER H, et al. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: Conjugated hypercholanemia without a clear clinical phenotype[J]. Hepatology, 2015, 61(1): 260-267. DOI: 10.1002/hep.27240.
    [8]
    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: 405-423. DOI: 10.1038/gim.2015.30.
    [9]
    SARGIACOMO C, EL-KEHDY H, POURCHER G, et al. Age-dependent glycosylation of the sodium taurocholate cotransporter polypeptide: From fetal to adult human livers[J]. Hepatol Commun, 2018, 2(6): 693-702. DOI: 10.1002/hep4.1174.
    [10]
    DENG M, MAO M, GUO L, et al. Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency[J]. Exp Ther Med, 2016, 12(5): 3294-3300. DOI: 10.3892/etm.2016.3752.
    [11]
    LIU R, CHEN C, XIA X, et al. Homozygous p. Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine[J]. Sci Rep, 2017, 7(1): 9214. DOI: 10.1038/s41598-017-07012-2.
    [12]
    QIU JW, DENG M, CHENG Y, et al. Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia[J]. Oncotarget, 2017, 8(63): 106598-106607. DOI: 10.18632/oncotarget.22503.
    [13]
    SONG YZ, DENG M. Sodium taurocholate cotransporting polypeptide deficiency manifesting as cholestatic jaundice in early infancy: A complicated case study[J]. Chin J Contemp Pediatr, 2017, 19(3): 350-354. DOI: 10.7499/j.issn.1008-8830.2017.03.020.

    宋元宗, 邓梅. 疑难病研究——钠牛磺胆酸共转运多肽缺陷病表现为婴儿早期胆汁淤积性黄疸[J]. 中国当代儿科杂志, 2017, 19(3): 350-354. DOI: 10.7499/j.issn.1008-8830.2017.03.020.
    [14]
    LI H, QIU JW, LIN GZ, et al. Clinical and genetic analysis of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency[J]. Chin J Contemp Pediatr, 2018, 20(4): 279-284. DOI: 10.7499/j.issn.1008-8830.2018.04.005.

    李华, 邱建武, 林桂枝, 等. 一例钠牛磺胆酸共转运多肽缺陷病患儿临床和遗传学分析[J]. 中国当代儿科杂志, 2018, 20(4): 279-284. DOI: 10.7499/j.issn.1008-8830.2018.04.005.
    [15]
    TAN HJ, DENG M, QIU JW, et al. Monozygotic twins suffering from sodium taurocholate cotransporting polypeptide deficiency: A case report[J]. Front Pediatr, 2018, 6: 354. DOI: 10.3389/fped.2018.00354.
    [16]
    LI H, DENG M, GUO L, et al. Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c. 595A > C (p. Ser199Arg)[J]. Mol Med Rep, 2019, 20(6): 4915-4924. DOI: 10.3892/mmr.2019.10763.
    [17]
    LIN H, QIU JW, RAUF YM, et al. Sodium taurocholate cotransporting polypeptide (NTCP) deficiency hidden behind citrin deficiency in early infancy: A report of three cases[J]. Front Genet, 2019, 10: 1108. DOI: 10.3389/fgene.2019.01108.
    [18]
    DONG C, ZHANG BP, WANG H, et al. Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients[J]. Medicine (Baltimore), 2019, 98(39): e17305. DOI: 10.1097/MD.0000000000017305.
    [19]
    YAN YY, WANG MX, GONG JY, et al. Abnormal bilirubin metabolism in patients with sodium taurocholate cotransporting polypeptide deficiency[J]. J Pediatr Gastroenterol Nutr, 2020, 71(5): e138-e141. DOI: 10.1097/MPG.0000000000002862.
    [20]
    ZOU TT, ZHU Y, WAN CM, et al. Clinical features of sodium-taurocholate cotransporting polypeptide deficiency in pediatric patients: Case series and literature review[J]. Transl Pediatr, 2021, 10(4): 1045-1054. DOI: 10.21037/tp-20-360.
    [21]
    SUN WF, YU F. Clinical analysis of two pediatric patients with sodium taurocholate cotransporting polypeptide deficiency[J]. China Med Herald, 2020, 17(17): 185-188. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202017046.htm

    孙文君, 于飞. 2例钠牛磺胆酸共转运多肽缺陷病患儿临床分析[J]. 中国医药导报, 2020, 17(17): 185-188. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202017046.htm
    [22]
    SONG YZ. Research advances in the pathogenesis, clinical manifestations, and diagnosis/treatment of sodium-taurocholate cotransporting polypeptide deficiency[J]. J Clin Hepatol, 2019, 35(8): 1690-1692. DOI: 10.3969/j.issn.1001-5256.2019.08.007.

    宋元宗. 钠牛磺胆酸共转运多肽缺陷病的发病机制、临床表现及诊疗进展[J]. 临床肝胆病杂志, 2019, 35(8): 1690-1692. DOI: 10.3969/j.issn.1001-5256.2019.08.007.
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