A Rare Coexistence of Biliary Atresia and Alagille Syndrome in a Neonate: Clinical Implications of Dual Etiology in Neonatal Cholestasis

Background and Clinical Significance: Biliary atresia (BA) and Alagille syndrome (ALGS) represent distinct anatomic and genetic causes of neonatal cholestasis. Their overlapping clinical, biochemical, and early histological features present a formidable diagnostic challenge in early infancy, and their simultaneous coexistence is exceedingly rare. This report documents a unique case of dual diagnosis to highlight the associated diagnostic pitfalls and implications for surgical management. Case Presentation: We present the case of a Taiwanese male neonate who manifested prolonged jaundice and acholic stools. Preoperative imaging and intraoperative cholangiography confirmed biliary atresia, for which the patient underwent a Kasai portoenterostomy. The patient subsequently exhibited an atypical postoperative course characterized by persistent hyperbilirubinemia and intractable pruritus. This atypical trajectory prompted an extensive, multisystem evaluation and molecular genetic analysis, revealing a concurrent genetic diagnosis of Alagille syndrome. To our knowledge, this dual diagnosis is rarely reported in the literature, which creates a significant challenge in determining surgical candidacy and predicting long-term liver health outcomes. Discussions: Early differentiation is complicated by the fact that some ALGS patients can initially mimic BA. Beyond its exceptional rarity, this case holds profound clinical significance for the evaluation of neonatal cholestasis, serving as a stark reminder of the risks of “diagnostic premature closure.” In diagnostically challenging cases of neonatal cholestasis, intraoperative biliary exploration remains the gold standard for the timely diagnosis of BA. Genetic testing should be considered an adjunctive tool when clinical and histological findings are inconclusive. Conclusions: This case highlights a critical clinical caveat in neonatal cholestasis: while a confirmed diagnosis of anatomical BA typically stands alone as a solitary pathology, clinicians should remain mindful of the remote possibility of a concurrent genetic etiology like ALGS in highly atypical presentations. Persistently unexpected postoperative jaundice or the accumulation of multisystem anomalies should prompt an expansion of the differential diagnosis. Recognizing this rare coexistence is crucial for effective multidisciplinary management, informed surgical decision-making, and accurate genetic counseling.