Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Oct;17(5):1098-1112.
doi: 10.1007/s12072-023-10578-x. Epub 2023 Aug 16.

Management of adults with Alagille syndrome

Mohammed D Ayoub #  1   2 , Ahmad A Bakhsh #  2   3 , Shannon M Vandriel  2 , Verena Keitel  4 , Binita M Kamath  5
Affiliations
Review

Management of adults with Alagille syndrome

Mohammed D Ayoub et al. Hepatol Int. 2023 Oct.

Abstract

Alagille syndrome (ALGS) is a complex rare genetic disorder that involves multiple organ systems and is historically regarded as a disease of childhood. Since it is inherited in an autosomal dominant manner in 40% of patients, it carries many implications for genetic counselling of patients and screening of family members. In addition, the considerable variable expression and absence of a clear genotype-phenotype correlation, results in a diverse range of clinical manifestations, even in affected individuals within the same family. With recent therapeutic advancements in cholestasis treatment and the improved survival rates with liver transplantation (LT), many patients with ALGS survive into adulthood. Although LT is curative for liver disease secondary to ALGS, complications secondary to extrahepatic involvement remain problematic lifelong. This review is aimed at providing a comprehensive review of ALGS to adult clinicians who will take over the medical care of these patients following transition, with particular focus on certain aspects of the condition that require lifelong surveillance. We also provide a diagnostic framework for adult patients with suspected ALGS and highlight key aspects to consider when determining eligibility for LT in patients with this syndrome.

Keywords: Bile duct paucity; Cholestatic liver disease; Hepatocellular carcinoma; JAG1; Liver transplant; Maralixibat; NOTCH2; Portal hypertension; Pruritus; Regenerative nodules.

PubMed Disclaimer

Conflict of interest statement

MDA, AAB, and VK declare they have no financial interests to declare. SMV is a consultant for Mirum and Albireo. BMK is a consultant for Mirum, Albireo, and Audentes (Astellas). BMK received unrestricted educational grant funding from Mirum and Albireo.

Figures

Fig. 1
Fig. 1
Spectrum of clinical features in Alagille syndrome
See this image and copyright information in PMC

References

    1. Alagille D, Habib E, Thomassin N. L'atresie des voies biliaires intrahepatiques avec voies biliaires extrahepatiques permeables chez l'enfant. J Par Pediatr. 1969;301:301–318. - PubMed
    1. Li L, Krantz ID, Deng Y, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16(3):243–251. doi: 10.1038/ng0797-243. - DOI - PubMed
    1. Oda T, Elkahloun AG, Pike BL, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16(3):235–242. doi: 10.1038/ng0797-235. - DOI - PubMed
    1. McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006;79(1):169–173. doi: 10.1086/505332. - DOI - PMC - PubMed
    1. Schindler EA, Gilbert MA, Piccoli DA, Spinner NB, Krantz ID, Loomes KM. Alagille syndrome and risk for hepatocellular carcinoma: Need for increased surveillance in adults with mild liver phenotypes. Amer J Med Genet Part A. 2021;185(3):719–731. doi: 10.1002/ajmg.a.62028. - DOI - PMC - PubMed