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Alagille Syndrome

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Diseases of the Liver in Children

Abstract

The Alagille syndrome is a multisystem developmental disease caused by mutations in Notch signaling pathway genes; typically JAG1 and very rarely NOTCH2. The syndrome is characterized by a wide variety of affected organs, including liver, heart, kidney, eye, spine, vasculature, and face. Within each organ, there are a range of abnormalities sometimes ranging from trivial to fatal. The most severe end of the spectrum of liver disease in Alagille syndrome is marked by profound cholestasis, with intense pruritus, hypercholesterolemia, xanthomas, jaundice, and fat malabsorption. Liver transplantation is successful at treating and curing the liver disease, but other systemic manifestations persist or progress. The identification of JAG1 as the cause in over 90 % and NOTCH2 in approximately 1 % has led to tremendous advances in understanding the pathogenesis of ALGS and also normal development. Analysis of mutation carriers has greatly expanded the number and the spectrum of Alagille syndrome patients and provided useful precision for family planning.

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Abbreviations

JAG1 :

Italicized gene

Notch:

Signaling pathway

Notch:

Receptor

NOTCH2, NOTCH3 :

Italicized gene

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Author information

Authors and Affiliations

  1. Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada

    Binita M. Kamath MBBChir

  2. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, 324 South 34th St, 7 NW 23, Philadelphia, PA, 19096, USA

    David A. Piccoli MD

Authors
  1. Binita M. Kamath MBBChir
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  2. David A. Piccoli MD
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Corresponding author

Correspondence to David A. Piccoli MD .

Editor information

Editors and Affiliations

  1. University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, Washington, USA

    Karen F. Murray

  2. University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, Washington, USA

    Simon Horslen

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Kamath, B.M., Piccoli, D.A. (2014). Alagille Syndrome. In: Murray, K., Horslen, S. (eds) Diseases of the Liver in Children. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9005-0_11

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  • DOI: https://doi.org/10.1007/978-1-4614-9005-0_11

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