Advertisement

The Renal Sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development

  • René RomeroEmail author
Chapter

Abstract

The renal manifestations of Alagille syndrome (ALGS) are an under-recognized, but clinically important component of the syndrome. Abnormalities in the Notch signaling pathway as a consequence of JAG1 and NOTCH2 mutations result in the diverse manifestations of ALGS. Notch signaling plays a central role in the development of multiple tissues and organs but particularly of the kidneys. Understanding the role of Notch signaling in renal development helps inform clinicians as to the more common renal findings in ALGS and the expectation of renal disease in these patients. Additionally, the Notch signal pathway plays a role in the evolution of chronic renal injury. How that response to renal injury is altered in ALGS and its impact on the clinical sequelae in ALGS is not known. Given the frequency of renal findings in ALGS, kidney specialists should form part of the multidisciplinary care team for these patients.

Keywords

Alagille syndrome Kidney Renal JAG1 Notch Development Manifestations Sequelae 

References

  1. 1.
    Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987;110(2):195–200.Google Scholar
  2. 2.
    Spinner NB, Leonard LD, Krantz ID. Alagille syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.Google Scholar
  3. 3.
    Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Human Genet. 2012;20(3):251–7.Google Scholar
  4. 4.
    Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16(3):243–51.PubMedPubMedCentralGoogle Scholar
  5. 5.
    McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the NOTCH signaling pathway. Am J Hum Genet. 2006;79(1):169–73.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16(3):235–42.Google Scholar
  7. 7.
    Kamath BM, Podkameni G, Hutchinson AL, Leonard LD, Gerfen J, Krantz ID, et al. Renal anomalies in Alagille syndrome: a disease-defining feature. Am J Med Genet A. 2012;158a(1):85–9.PubMedGoogle Scholar
  8. 8.
    Kamath BM, Spinner NB, Rosenblum ND. Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol. 2013;9(7):409–18.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez-Lara PA, Piccoli DA, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27(5):436–43.Google Scholar
  10. 10.
    Bauer RC, Laney AO, Smith R, Gerfen J, Morrissette JJ, Woyciechowski S, et al. Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Hum Mutat. 2010;31(5):594–601.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Harendza S, Hubner CA, Glaser C, Burdelski M, Thaiss F, Hansmann I, et al. Renal failure and hypertension in Alagille syndrome with a novel JAG1 mutation. J Nephrol. 2005;18(3):312–7.PubMedGoogle Scholar
  12. 12.
    Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB. Consequences of JAG1 mutations. J Med Genet. 2003;40(12):891–5.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Krantz ID. Alagille syndrome: chipping away at the tip of the iceberg. Am J Med Genet. 2002;112(2):160–2.PubMedGoogle Scholar
  14. 14.
    Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology. 1999;29(3):822–9.Google Scholar
  15. 15.
    Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, et al. Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital. J Pediatr Gastroenterol Nutr. 2011;52(1):84–9.Google Scholar
  16. 16.
    Quiros-Tejeira RE, Ament ME, Heyman MB, Martin MG, Rosenthal P, Hall TR, et al. Variable morbidity in alagille syndrome: a review of 43 cases. J Pediatr Gastroenterol Nutr. 1999;29(4):431–7.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Hoffenberg EJ, Narkewicz MR, Sondheimer JM, Smith DJ, Silverman A, Sokol RJ. Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr. 1995;127(2):220–4.Google Scholar
  18. 18.
    Bray SJ. Notch signalling in context. Nat Rev Mol Cell Biol. 2016;17(11):722–35.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Masek J, Andersson ER. The developmental biology of genetic Notch disorders. Development. 2017;144(10):1743–63.PubMedGoogle Scholar
  20. 20.
    Gridley T. Notch signaling and inherited disease syndromes. Human Mol Genet. 2003;12 Spec No 1:R9–13.Google Scholar
  21. 21.
    Kopan R, Chen S, Liu Z. Alagille, Notch, and robustness: why duplicating systems does not ensure redundancy. Pediatr Nephrol. 2014;29(4):651–7.PubMedGoogle Scholar
  22. 22.
    Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216–33.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Sirin Y, Susztak K. Notch in the kidney: development and disease. J Pathol. 2012;226(2):394–403.PubMedGoogle Scholar
  24. 24.
    Nicolaou N, Renkema KY, Bongers EM, Giles RH, Knoers NV. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat Rev Nephrol. 2015;11(12):720–31.PubMedGoogle Scholar
  25. 25.
    Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J. Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990–1998). Arch Gynecol Obstet. 2002;266(3):163–7.PubMedGoogle Scholar
  26. 26.
    Chesnaye N, Bonthuis M, Schaefer F, Groothoff JW, Verrina E, Heaf JG, et al. Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry. Pediatr Nephrol. 2014;29(12):2403–10.PubMedGoogle Scholar
  27. 27.
    Wuhl E, van Stralen KJ, Verrina E, Bjerre A, Wanner C, Heaf JG, et al. Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin J Am Soc Nephrol. 2013;8(1):67–74.PubMedGoogle Scholar
  28. 28.
    Hoy WE, Bertram JF, Denton RD, Zimanyi M, Samuel T, Hughson MD. Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens. 2008;17(3):258–65.PubMedGoogle Scholar
  29. 29.
    Vivante A, Kohl S, Hwang DY, Dworschak GC, Hildebrandt F. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr Nephrol. 2014;29(4):695–704.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Cebrian C, Borodo K, Charles N, Herzlinger DA. Morphometric index of the developing murine kidney. Dev Dyn. 2004;231(3):601–8.Google Scholar
  31. 31.
    Saxen L, Sariola H. Early organogenesis of the kidney. Pediatr Nephrol. 1987;1(3):385–92.PubMedGoogle Scholar
  32. 32.
    Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 2010;18(5):698–712.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Pietila I, Vainio SJ. Kidney development: an overview. Nephron Exp Nephrol. 2014;126(2):40.PubMedGoogle Scholar
  34. 34.
    Schedl A. Renal abnormalities and their developmental origin. Nat Rev Genet. 2007;8(10):791–802.PubMedGoogle Scholar
  35. 35.
    Schell C, Wanner N, Huber TB. Glomerular development--shaping the multi-cellular filtration unit. Semin Cell Dev Biol. 2014;36:39–49.PubMedGoogle Scholar
  36. 36.
    Blake J, Rosenblum ND. Renal branching morphogenesis: morphogenetic and signaling mechanisms. Semin Cell Dev Biol. 2014;36:2–12.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Cheng HT, Kopan R. The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney. Kidney Int. 2005;68(5):1951–2.PubMedGoogle Scholar
  38. 38.
    McCright B, Gao X, Shen L, Lozier J, Lan Y, Maguire M, et al. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development. 2001;128(4):491–502.Google Scholar
  39. 39.
    Weinmaster G, Roberts VJ, Lemke G. Notch2: a second mammalian Notch gene. Development. 1992;116(4):931–41.PubMedGoogle Scholar
  40. 40.
    McCright B. Notch signaling in kidney development. Curr Opin Nephrol Hypertens. 2003;12(1):5–10.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Chen L, Al-Awqati Q. Segmental expression of Notch and Hairy genes in nephrogenesis. Am J Physiol Renal Physiol. 2005;288(5):F939–52.PubMedGoogle Scholar
  42. 42.
    Piscione TD, Wu MY, Quaggin SE. Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis. Gene Expr Patterns. 2004;4(6):707–11.PubMedGoogle Scholar
  43. 43.
    Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, et al. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007;134(4):801–11.PubMedPubMedCentralGoogle Scholar
  44. 44.
    McCright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development. 2002;129(4):1075–82.Google Scholar
  45. 45.
    Wang P, Pereira FA, Beasley D, Zheng H. Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development. 2003;130(20):5019–29.PubMedGoogle Scholar
  46. 46.
    Cheng HT, Miner JH, Lin M, Tansey MG, Roth K, Kopan R. Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development. 2003;130(20):5031–42.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007;445(7129):776–80.PubMedGoogle Scholar
  48. 48.
    Fujimura S, Jiang Q, Kobayashi C, Nishinakamura R. Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol. 2010;21(5):803–10.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Bonegio RG, Beck LH, Kahlon RK, Lu W, Salant DJ. The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development. Kidney Int. 2011;79(10):1099–112.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Jeong HW, Jeon US, Koo BK, Kim WY, Im SK, Shin J, et al. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest. 2009;119(11):3290–300.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Gray MJ, Kim CA, Bertola DR, Arantes PR, Stewart H, Simpson MA, et al. Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome. Eur J Hum Genet. 2012;20(1):122–4.PubMedGoogle Scholar
  52. 52.
    Surendran K, Boyle S, Barak H, Kim M, Stomberski C, McCright B, et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol. 2010;337(2):386–95.PubMedGoogle Scholar
  53. 53.
    Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008;14(3):290–8.PubMedGoogle Scholar
  54. 54.
    Liu M, Ning X, Li R, Yang Z, Yang X, Sun S, et al. Signalling pathways involved in hypoxia-induced renal fibrosis. J Cell Mol Med. 2017;21(7):1248–59.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK. Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol. 2010;298(5):F1078–94.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, Kuwahara M, et al. Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int. 2008;73(11):1240–50.PubMedGoogle Scholar
  57. 57.
    Gupta S, Li S, Abedin MJ, Wang L, Schneider E, Najafian B, et al. Effect of Notch activation on the regenerative response to acute renal failure. Am J Physiol Renal Physiol. 2010;298(1):F209–15.PubMedGoogle Scholar
  58. 58.
    Murea M, Park JK, Sharma S, Kato H, Gruenwald A, Niranjan T, et al. Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function. Kidney Int. 2010;78(5):514–22.PubMedGoogle Scholar
  59. 59.
    Asanuma K, Oliva Trejo JA, Tanaka E. The role of Notch signaling in kidney podocytes. Clin Exp Nephrol. 2017;21(1):1–6.PubMedGoogle Scholar
  60. 60.
    Walsh DW, Roxburgh SA, McGettigan P, Berthier CC, Higgins DG, Kretzler M, et al. Co-regulation of Gremlin and Notch signalling in diabetic nephropathy. Biochim Biophys Acta. 2008;1782(1):10–21.PubMedGoogle Scholar
  61. 61.
    Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, et al. Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest. 2010;120(11):4040–54.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Sorensen-Zender I, Rong S, Susnik N, Zender S, Pennekamp P, Melk A, et al. Renal tubular Notch signaling triggers a prosenescent state after acute kidney injury. Am J Physiol Renal Physiol. 2014;306(8):F907–15.PubMedGoogle Scholar
  63. 63.
    Edeling M, Ragi G, Huang S, Pavenstadt H, Susztak K. Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog. Nat Rev Nephrol. 2016;12(7):426–39.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Ying Q, Wu G. Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update. Development. 2017;39(1):474–83.Google Scholar
  65. 65.
    Niranjan T, Murea M, Susztak K. The pathogenic role of Notch activation in podocytes. Nephron Exp Nephrol. 2009;111(4):e73–9.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Sharma M, Callen S, Zhang D, Singhal PC, Vanden Heuvel GB, Buch S. Activation of Notch signaling pathway in HIV-associated nephropathy. AIDS. 2010;24(14):2161–70.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Lykavieris P, Hadchouel M, Chardot C, Bernard O. Outcome of liver disease in children with Alagille syndrome: a study of 163 patients. Gut. 2001;49(3):431–5.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Habib R, Dommergues JP, Gubler MC, Hadchouel M, Gautier M, Odievre M, et al. Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia). Pediatr Nephrol. 1987;1(3):455–64.PubMedGoogle Scholar
  69. 69.
    Rosenthal IM, Spellberg MA, McGrew EA, Rozenfeld IH. Absence of interlobular bile ducts. Report of a case of probable intrahepatic bile duct agenesis with severe hypercholesterolemia, xanthomatosis, and glomerular lipid deposition. Am J Dis child. 1961;101:228–37.PubMedGoogle Scholar
  70. 70.
    Davis J, Griffiths R, Larkin K, Rozansky D, Troxell M. Glomerular basement membrane lipidosis in Alagille syndrome. Pediatr Nephrol. 2010;25(6):1181–4.PubMedGoogle Scholar
  71. 71.
    Benoit G, Sartelet H, Levy E, Boule ME, Alvarez F, Abed L, et al. Mesangiolipidosis in Alagille syndrome--relationship with apolipoprotein A-I. Nephrol Dial Transplant. 2007;22(7):2072–5.PubMedGoogle Scholar
  72. 72.
    Bissonnette MLZ, Lane JC, Chang A. Extreme renal pathology in Alagille syndrome. Kidney Int Rep. 2017;2(3):493–7.PubMedGoogle Scholar
  73. 73.
    Wang H, Wang X, Li Q, Chen S, Liu L, Wei Z, et al. Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome. Gene. 2012;499(1):191–3.PubMedGoogle Scholar
  74. 74.
    Jurkiewicz D, Gliwicz D, Ciara E, Gerfen J, Pelc M, Piekutowska-Abramczuk D, et al. Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome. J Appl Genet. 2014;55(3):329–36.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Brennan A, Kesavan A. Novel Heterozygous Mutations in JAG1 and NOTCH2 Genes in a Neonatal Patient with Alagille Syndrome. Case Rep Pediatr. 2017;2017:1368189.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Hannoush ZC, Puerta H, Bauer MS, Goldberg RB. New JAG1 mutation causing Alagille syndrome presenting with severe hypercholesterolemia: case report with emphasis on genetics and lipid abnormalities. J Clin Endocrinol Metab. 2017;102(2):350–3.PubMedGoogle Scholar
  77. 77.
    Jacquet A, Guiochon-Mantel A, Noel LH, Sqalli T, Bedossa P, Hadchouel M, et al. Alagille syndrome in adult patients: it is never too late. Am J Kidney Dis. 2007;49(5):705–9.PubMedGoogle Scholar
  78. 78.
    Berrocal T, Gamo E, Navalon J, Prieto C, Al-Assir I, Cortes P, et al. Syndrome of Alagille: radiological and sonographic findings. A review of 37 cases. Eur Radiol. 1997;7(1):115–8.PubMedGoogle Scholar
  79. 79.
    Devriendt K, Dooms L, Proesmans W, de Zegher F, Desmet V, Eggermont E. Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: atypical Alagille syndrome? Eur J Pediatr. 1996;155(2):87–90.PubMedGoogle Scholar
  80. 80.
    Tolia V, Dubois RS, Watts FB Jr, Perrin E. Renal abnormalities in paucity of interlobular bile ducts. J Pediatr Gastroenterol Nutr. 1987;6(6):971–6.PubMedGoogle Scholar
  81. 81.
    Yucel H, Hoorntje SJ, Bravenboer B. Renal abnormalities in a family with Alagille syndrome. Neth J Med. 2010;68(1):38–9.PubMedGoogle Scholar
  82. 82.
    Hyams JS, Berman MM, Davis BH. Tubulointerstitial nephropathy associated with arteriohepatic dysplasia. Gastroenterology. 1983;85(2):430–4.PubMedGoogle Scholar
  83. 83.
    Wolfish NM, Shanon A. Nephropathy in arteriohepatic dysplasia (Alagille's syndrome). Child Nephrol Urol. 1988;9(3):169–72.PubMedGoogle Scholar
  84. 84.
    Hayashi N, Okuyama H, Matsui Y, Yamaya H, Kinoshita E, Minato H, et al. Adult-onset renal failure in a family with Alagille syndrome with proteinuria and a novel JAG1 mutation. Clin Kidney J. 2013;6(3):295–9.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Martin SR, Garel L, Alvarez F. Alagille's syndrome associated with cystic renal disease. Arch Dis Child. 1996;74(3):232–5.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Pombo F, Isla C, Gayol A, Bargiela A. Aortic calcification and renal cysts demonstrated by CT in a teenager with Alagille syndrome. Pediatr Radiol. 1995;25(4):314–5.PubMedGoogle Scholar
  87. 87.
    Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, et al. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109(11):1354–8.Google Scholar
  88. 88.
    Uyttendaele H, Ho J, Rossant J, Kitajewski J. Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium. Proc Natl Acad Sci U S A. 2001;98(10):5643–8.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Xue Y, Gao X, Lindsell CE, Norton CR, Chang B, Hicks C, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet. 1999;8(5):723–30.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Salem JE, Bruguiere E, Iserin L, Guiochon-Mantel A, Plouin PF. Hypertension and aortorenal disease in Alagille syndrome. J Hypertens. 2012;30(7):1300–6.PubMedGoogle Scholar
  91. 91.
    Kohaut J, Pommier R, Guerin F, Pariente D, Jacquemin E, Martelli H, et al. Abdominal arterial anomalies in children with Alagille syndrome: surgical aspects and outcomes of liver transplantation. J Pediatr Gastroenterol Nutr. 2017;64(6):888–91.PubMedGoogle Scholar
  92. 92.
    Hirai H, Santo Y, Kogaki S, Kurotobi S, Etani Y, Mushiake S, et al. Successful stenting for renal artery stenosis in a patient with Alagille syndrome. Pediatr Nephrol. 2005;20(6):831–3.PubMedGoogle Scholar
  93. 93.
    Ahn KJ, Yoon JK, Kim GB, Kwon BS, Go JM, Moon JS, et al. Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center. Korean J Pediatr. 2015;58(10):392–7.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Berard E, Sarles J, Triolo V, Gagnadoux MF, Wernert F, Hadchouel M, et al. Renovascular hypertension and vascular anomalies in Alagille syndrome. Pediatr Nephrol. 1998;12(2):121–4.PubMedGoogle Scholar
  95. 95.
    Shrivastava R, Williams A, Mikhail A, Roberts D, Richards M, Aithal V. An unusual cause of hypertension and renal failure: a case series of a family with Alagille syndrome. Nephrol Dial Transplant. 2010;25(5):1501–6.PubMedGoogle Scholar
  96. 96.
    Schonck M, Hoorntje S, van Hooff J. Renal transplantation in Alagille syndrome. Nephrol Dial Transplant. 1998;13(1):197–9.PubMedGoogle Scholar
  97. 97.
    Schwarzenberg SJ, Grothe RM, Sharp HL, Snover DC, Freese D. Long-term complications of arteriohepatic dysplasia. Am J Med. 1992;93(2):171–6.PubMedGoogle Scholar
  98. 98.
    Maisonneuve E, Morin F, Crochetiere C, Lemyre E, Bigras JL, Leduc L, et al. Multidisciplinary management of a hepatic and renal transplant patient with Alagille syndrome. Int J Obstet Anesth. 2012;21(4):382–3.PubMedGoogle Scholar
  99. 99.
    Kamath BM, Yin W, Miller H, Anand R, Rand EB, Alonso E, et al. Outcomes of liver transplantation for patients with Alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transplant. 2012;18(8):940–8.Google Scholar
  100. 100.
    Arnon R, Annunziato R, Miloh T, Suchy F, Sakworawich A, Sogawa H, et al. Orthotopic liver transplantation for children with Alagille syndrome. Pediatr Transplant. 2010;14(5):622–8.Google Scholar
  101. 101.
    Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Hepatology. J Pediatr Gastroenterol Nutr. 2014;60(1):362–98.Google Scholar
  102. 102.
    Kelly DA, Bucuvalas JC, Alonso EM, Karpen SJ, Allen U, Green M, et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transplant. 2013;19(8):798–825.Google Scholar
  103. 103.
    Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;50(6):580–6.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Kamath BM, Munoz PS, Bab N, Baker A, Chen Z, Spinner NB, et al. A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;50(5):526–30.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Mouzaki M, Bass LM, Sokol RJ, Piccoli DA, Quammie C, Loomes KM, et al. Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome. Liver Int. 2016;36(5):755–60.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Elisofon SA, Emerick KM, Sinacore JM, Alonso EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51(6):759–65.Google Scholar
  107. 107.
    Kamath BM, Chen Z, Romero R, Fredericks EM, Alonso EM, Arnon R, et al. Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome. The Journal of pediatrics. 2015;167(2):390–6.e3.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Wang JS, Wang XH, Zhu QR, Wang ZL, Hu XQ, Zheng S. Clinical and pathological characteristics of Alagille syndrome in Chinese children. World J Pediatr. 2008;4(4):283–8.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and NutritionEmory University School of Medicine, Children’s Healthcare of Atlanta-EglestonAtlantaUSA

Personalised recommendations