Abstract
Alagille syndrome (ALGS) is a multisystem disease characterized by cholestasis and bile duct paucity on liver biopsy in addition to variable involvement of the heart, eyes, skeleton, face, kidneys, and vasculature. The identification of JAG1 and NOTCH2 as disease-causing genes has deepened our understanding of the molecular mechanisms underlying ALGS. However, the variable expressivity of the clinical phenotype and the lack of genotype-phenotype relationships creates significant diagnostic and therapeutic challenges. In this review, we provide a comprehensive overview of the clinical characteristics and management of ALGS, and the molecular basis of ALGS pathobiology. We further describe unique diagnostic considerations that pose challenges to clinicians and outline therapeutic concepts and treatment targets that may be available in the near future.
Highlights
Alagille syndrome (ALGS) is an inherited multi-organ disease of variable severity
In an effort to avoid a Kasai procedure in ALGS when nuclear scans, cholangiographic, and histologic studies are inconclusive, time permitting, clinicians should opt for expedited mutational analysis for JAG1 and NOTCH2 simultaneously which may be available in 3–4 weeks
Cholestasis-specific formulations exist for fat-soluble vitamin (FSV) supplementation (e.g., DEKAs), which may help with medication compliance and cost, especially in patients with multiple fat-soluble vitamin deficiency (FSVD)
Summary
Alagille syndrome (ALGS) is an inherited multi-organ disease of variable severity. The first clinical description of ALGS was made by the French hepatologist Daniel Alagille in 1969 who reported on 30 patients with hypoplastic intra-hepatic bile ducts, of which 50% appeared to have readily recognizable extrahepatic clinical features [1]. In 1987, Alagille reported on a larger series of 80 children with paucity of intra-hepatic bile ducts associated with variable degrees of chronic cholestasis, characteristic facial features, structural heart disease, posterior embryotoxon, and vertebral arch defects [2,3]. The incidence of clinically apparent ALGS is approximately 1 in 70,000 live births, but this was estimated based on the presence of neonatal cholestasis in the pre-molecular diagnostics era [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
