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

宋元宗

doi:10.3969/j.issn.1001-5256.2019.08.007

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

DOI: 10.3969/j.issn.1001-5256.2019.08.007

宋元宗

暨南大学附属第一医院儿科

基金项目:

国家自然科学基金(81741080)；

详细信息

中图分类号: R596.1
计量
- 文章访问数: 2056
- HTML全文浏览量: 58
- PDF下载量: 491
- 被引次数: 0
出版历程
- 收稿日期: 2019-06-10
- 出版日期: 2019-08-20

Research advances in the pathogenesis, clinical manifestations, and diagnosis/treatment of sodium-taurocholate cotransporting polypeptide deficiency

Song YuanZong

Department of Pediatrics, The First Affiliated Hospital of Jinan University

Research funding:

摘要

摘要: 钠牛磺胆酸共转运多肽(NTCP)缺陷病是SLC10A1双等位基因突变导致的一种新的遗传性胆汁酸代谢病,在我国可能并不罕见。NTCP缺陷病以儿童期显著而持续性的高胆汁酸血症为主要临床特征,并可能参与新生儿高胆红素血症、婴儿早期胆汁淤积症和妊娠胆汁淤积症的形成。NTCP缺陷病目前缺乏特异性治疗手段,但通常预后良好。SLC10A1基因分析有助于该病患者及时确诊,同时避免不必要的检查和干预。
- 代谢疾病 /
- 钠牛磺胆酸共转运多肽 /
- SLC10A1基因 /
- 胆汁淤积
Abstract: Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a new hereditary bile acid metabolic disease due to biallelic mutations of the SLC10 A1 gene and is not rare in China. Marked and persistent hypercholanemia in childhood is the major clinical feature of NTCP deficiency, and this condition might be involved in the development of neonatal hyperbilirubinemia, cholestasis in early infancy, and cholestasis in pregnancy. At present, there lack specific therapies for NTCP deficiency, but such patients tend to have good prognosis. SLC10 A1 gene detection may facilitate the timely and definite diagnosis of this disease and thus avoid unnecessary examinations and interventions.
- metabolic diseases /
- sodium-taurocholate cotransporting polypeptide /
- SLC10A1 gene /
- cholestasis

HTML全文

参考文献(33)

[1] BIJSMANS IT, BOUWMEESTER RA, GEYER J, et al. Homoand hetero-dimeric architecture of the human liver Na+-dependent taurocholate cotransporting protein[J]. Biochem, 2012, 441 (3) :1007-1015.

[2] 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.

[3] HAGENBUCH B, DAWSON P. The sodium bile salt cotransport family SLC10[J]. Pflugers Arch, 2004, 447 (5) :566-570.

[4] STIEGER B. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation[J]. Handb Exp Pharmacol, 2011, 201:205-259.

[5] WOLKOFF AW. Organic anion uptake by hepatocytes[J].Compr Physiol, 2014, 4 (4) :1715-1735.

[6] 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.

[7] ANWER MS, STIEGER B. Sodium-dependent bile salt transporters of the SLC10A transporter family:More than solutetransporters[J]. Pflugers Arch, 2014, 466 (1) :77-89.

[8] YAN H, ZHONG, XU G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J]. Elife, 2012, 1:e00049.

[9] SHIAO T, IWAHASHI M, FORTUNE J, et al. Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter[J]. Genomics, 2000, 69 (2) :203-213.

[10] JUNG D, HAGENBUCH B, FRIED M, et al. Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 286 (5) :g752-g761.

[11] HO RH, LEAKE BF, ROBERTS RL, et al. Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition[J]. J Biol Chem, 2004, 279 (8) :7213-7222.

[12] 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.

[13] 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.

[14] CHEN R, DENG M, RAUF YM, et al. Intrahepatic cholestasis of pregnancy as a clinical manifestation of sodium-taurocholate cotransporting polypeptide deficiency[J]. Tohoku J Exp Med, 2019, 248 (1) :57-61.

[15] 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. (in Chinese) 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.

[16] 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. (in Chinese) 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.

[17] PENG L, ZHAO Q, LI Q, et al. The p. Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B[J]. Hepatology, 2015, 61 (4) :1251-1260.

[18] PAN W, SONG IS, SHIN HJ, et al. Genetic polymorphisms in Na+-taurocholate co-transporting polypeptide (NTCP) and ileal apical sodium-dependent bile acid transporter (ASBT) and ethnic comparisons of functional variants of NTCP among Asian populations[J]. Xenobiotica, 2011, 41 (6) :501-510.

[19] 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.

[20] 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.

[21] 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.

[22] VAN HERPE F, WATERHAM HR, ADAMS CJ, et al. NTCP deficiency and persistently raised bile salts:An adult case[J]. J Inherit Metab Dis, 2017, 40 (3) :313-315.

[23] ERLINGER S, ARIAS IM, DHUMEAUX D. Inherited disorders of bilirubin transport and conjugation:New insights into molecular mechanisms and consequences[J]. Gastroenterology, 2014, 146 (7) :1625-1638.

[24] MOOIJ MG, SCHWARZ UI, de KONING BA, et al. Ontogeny of human hepatic and intestinal transporter gene expression during childhood:Age matters[J]. Drug Metab Dispos, 2014, 42 (8) :1268-1274.

[25] PRASAD B, EVERS R, GUPTA A, et al. Interindividual variability in hepatic organic anion-transporting polypeptides and P-glycoprotein (ABCB1) protein expression:Quantification by liquid chromatography tandem mass spectroscopy and influence of genotype, age, and sex[J]. Drug Metab Dispos, 2014, 42 (1) :78-88.

[26] ROSCAM ABBING RLP, SLIJEPCEVIC D, DONKERS JM, et al. Blocking sodium-taurocholate cotransporting polypeptide stimulates biliary cholesterol and phospholipid secretion[J].Hepatology, 2019.[Epub ahead of print]

[27] LI H, DENG M, GUO L, et al. Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the same novel SLC10A1 variant c. 595A> C (p. Ser199Arg) [J]. Mol Med Rep, 2019.[Accepted]

[28] BALISTRERI WF, SUCHY FJ, FARRELL MK, et al. Pathologic versus physiologic cholestasis:Elevated serum concentration of a secondary bile acid in the presence of hepatobiliary disease[J]. J Pediatr, 1981, 98 (3) :399-402.

[29] SUCHY FJ, BALISTRERI, HEUBI JE, et al. Physiologic cholestasis:Elevation of the primary serum bile acid concentrations in normal infants[J]. Gastroenterology, 1981, 80 (5 pt 1) :1037-1041.

[30] KAWASAKI H, YAMANISHI Y, MIYAKE M, et al. Age-and sex-related profiles of serum primary and total bile acids in infants, children and adults[J]. Tohoku J Exp Med, 1986, 150 (3) :353-357.

[31] POLKOWSKA G, POLKOWSKI W, KUDLICKA A, et al. Range of serum bile acid concentrations in neonates, infants, older children, and in adults[J]. Med Sci Monit, 2001, 7 (Suppl 1) :268-270.

[32] YAN H, PENG B, LIU Y, et al. Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide[J]. J Virol, 2014, 88 (6) :3273-3284.

[33] DENG M. Analysis of SLC10A1 gene variants and clinical features of the patients with sodium taurocholate cotransporting polypeptide (NTCP) deficiency[D]. Guangzhou:Jinan University, 2018. (in Chinese) 邓梅.钠牛磺胆酸共转运多肽缺陷病患者SLC10A1基因变异及临床特征研究[D].广州:暨南大学, 2018.

施引文献

资源附件(0)

访问统计