Abstract

ALAGILLE SYNDROME BEYOND CHILDHOOD: A BIBLIOMETRIC AND CLINICAL REAPPRAISAL OF A RARE GENETIC DISORDER

*Mahalakshmi M., Archana B., Kiruthiga O. B., Shanmuga Priya, Arul Prakasam K. C.

ABSTRACT

Background: Alagille Syndrome (ALGS) is a rare autosomal dominant multisystem disorder primarily caused by mutations in the JAG1 gene (94–95%) and less frequently in NOTCH2 (<2%). It affects various organs, including the liver, heart, eyes, skeleton, kidneys, and facial features. The hallmark hepatic feature is bile duct paucity, leading to cholestasis, pruritus, and progressive liver disease. Despite its classification as a pediatric disorder, ALGS often persists into adulthood with variable expression and complications, frequently resulting in misdiagnosis. Aim: This study aims to review and evaluate current knowledge on ALGS, focusing on its genetic basis, clinical spectrum, diagnostic challenges, therapeutic strategies, and future research directions. It also emphasizes hepatic involvement and the evolving role of advanced molecular diagnostics and novel treatment approaches. Methods: A bibliometric approach was used to analyze published literature on ALGS. Histopathological data from liver biopsies andgenetic findings, particularly JAG1 and NOTCH2 variants, were examined. Diagnostic criteria, therapeutic protocols, and outcomes were reviewed using peer-reviewed sources, with attention to advancements in pharmacological and surgical management. Results: ALGS shows a wide clinical spectrum, including cholestasis, congenital heart defects (notably pulmonary artery stenosis and Tetralogy of Fallot), butterfly vertebrae, ocular anomalies, and distinctive facial features. Approximately 15–30% of patients with liver involvement progress to severe disease necessitating liver transplantation. Novel therapies such as Maralixibat and Odevixibat have shown efficacy in managing pruritus. Experimental strategies including gene editing and patient-derived organoids are under investigation. Survival into adulthood exceeds 90% with adequate multidisciplinary care, though quality of life remains affected by chronic complications. Conclusion: Alagille Syndrome is a complex, multisystemic disorder requiring early diagnosis, ongoing monitoring, and tailored multidisciplinary care. Genetic testing is essential for accurate diagnosis, especially given the phenotypic variability. While medical and surgical treatments have improved outcomes, continued research into gene-targeted therapies holds promise for more definitive future interventions.

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