Coexistence of Alagille Syndrome and Biliary Atresia in a Neonate: A Case Report

Coexistence of Alagille Syndrome and Biliary Atresia in a Neonate: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Coexistence of Alagille Syndrome and Biliary Atresia in a Neonate: A Case Report Si Li, Xiangde Lin, Lili Ma, Xin Lei, Tingting You, Guoxian Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8128374/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Dec, 2025 Read the published version in BMC Pediatrics → Version 1 posted 12 You are reading this latest preprint version Abstract Background Alagille syndrome (ALGS) is an autosomal dominant disorder caused by gene mutations. Although its cholestatic manifestations may resemble those of biliary atresia (BA), the two conditions are distinct disease entities with fundamentally different pathogenesis, diagnostic approaches, and management strategies. Case Presentation We report a case of a female Han Chinese neonate with BA concomitant with ALGS. The diagnosis of ALGS was confirmed based on clinical manifestations and genetic testing findings. After conservative treatment failed to show improvement, operative exploration confirmed BA. The neonate underwent Kasai portoenterostomy and achieved successful recovery. Post-operative follow-up for over eight months has exhibited a favorable prognosis. Conclusion This is the first report of BA and ALGS co-existence. The concurrent presence of these two distinct hepatopathies creates significant diagnostic pitfalls, highlighting the imperative for heightened clinical vigilance to prevent misdiagnosis, delayed interventions, and inappropriate treatment. Alagille Syndrome Biliary Atresia neonate Background Alagille syndrome (ALGS) is an autosomal dominant multisystem disorder caused by pathogenic variants in JAG1 or NOTCH2, core components of the Notch signaling pathway [ 1 , 2 ] . In contrast, biliary atresia (BA) is an idiopathic, progressive cholangiopathy of infancy characterized by obliteration of the extrahepatic bile ducts [ 3 ] . Although both disorders present with cholestasis in infancy, their underlying pathogenesis, anatomical defects, and management strategies are fundamentally distinct. Notably, the phenotypic overlap can lead to misdiagnosis. Instances of ALGS being mistaken for BA have been reported, with one study suggesting that Kasai portoenterostomy may accelerate liver dysfunction in ALGS patients [ 4 ] . However, the true coexistence of both ALGS and BA in a single neonate has not been previously documented. Given their distinct pathogenic mechanisms and treatment approaches, accurate differentiation between these two entities is crucial. Herein, we report a unique case of concurrent ALGS and BA in a neonate, detailing the clinical presentation, diagnostic workup, and therapeutic management, with the aim of enhancing clinical recognition and guiding optimal management in such complex scenarios. Case presentation A 1-month-old infant was admitted with persistent jaundice, clay-colored stools, and abdominal distension. Physical examination revealed moderate icteric sclerae and skin, along with distinctive facial features including a broad forehead, deep-set eyes with hypertelorism, a straight nasal bridge, a pointed chin, and a characteristic triangular facies (Fig. 1 ). Abdominal examination showed distension with the liver palpable 2.5 cm below the right costal margin. Laboratory investigations demonstrated significant conjugated hyperbilirubinemia: total bilirubin 123.8 µmol/L, direct bilirubin 96.3 µmol/L. Liver enzymes were markedly elevated with ALT 451.8 U/L, AST 409.2 U/L, GGT 766.0 U/L, and ALP 456.3 U/L. Serum matrix metalloproteinase-7 (MMP-7) was elevated at 118.74 ng/ml. Genetic testing identified a heterozygous pathogenic variant in the JAG1 gene, consistent with Alagille syndrome type 1. Familial genetic screening revealed the same heterozygous JAG1 mutation in the father, while the mother showed no abnormalities. Abdominal ultrasound with shear wave elastography showed hepatomegaly (liver extending 2.4 cm below right costal margin) with increased parenchymal echogenicity and echo enhancement of the Greenson sheath. The gallbladder and common bile duct were not visualized. After 3 weeks of treatment with glutathione, diammonium glycyrrhizate and ursodeoxycholic acid, the jaundice showed minimal improvement, and the stools remained acholic. Laparoscopic exploration revealed a mildly enlarged liver with a dark color and tough texture. Spider nevus-like capillary dilatation was observed on the surface of the liver, and a striated gallbladder measuring approximately 1.0 cm × 0.3 cm was identified (Fig. 2 ). The gallbladder fundus was incised, revealing a solid, non-lumenal structure, so the cholangiogram was not possible. Intraoperative diagnosis: 1. BA; 2. ALGS. Following the Kasai portoenterostomy, the postoperative regimen comprised cefoperazone, sulbactam, glutathione, glycyrrhizinate, ursodeoxycholic acid, methylprednisolone, intravenous fluid and high nutritional status support. After the operation, the yellow skin and sclera of the child disappeared significantly, and the stool turned yellow. Postoperative pathological findings were consistent with cholestasis and BA (Fig. 3 ). After 8 months of follow-up, there was no yellow staining on the skin or sclera, and the color of the stool is normal. Biochemical and ultrasound examinations have not shown any significant abnormalities. Discussion and conclusion We herein report a rare case of ALGS associated with BA in infancy and explains the diagnosis, treatment process and follow-up prognosis of this case in detail. This study provides clues for the potential and under-recognized pathophysiological intersections or synergistic pathogenic mechanisms of ALGS and BA, broadens the differential diagnostic thinking in children with complex cholestasis, and provides new research ideas for in-depth exploration of whether ALGS and BA have common or mutually affecting genetic susceptibility, molecular pathways, and pathogenesis. The pathogenic mechanisms underlying ALGS and BA are fundamentally distinct. ALGS is directly attributable to pathogenic variants in JAG1 or NOTCH2, leading to multisystem involvement. In contrast, the etiology of BA remains elusive, potentially involving viral triggers, immune dysregulation, or environmental factors in a multifactorial model. Anatomically, ALGS is characterized by intrahepatic bile duct paucity, whereas BA presents with a complete obliteration of the extrahepatic biliary tree. This anatomical distinction underpins their divergent management strategies: BA necessitates prompt surgical intervention like the Kasai procedure to restore bile flow, while management of ALGS is primarily supportive, with liver transplantation reserved for end-stage liver disease. Notably, previous reports have indicated that performing Kasai portoenterostomy in patients misdiagnosed with BA but later confirmed to have isolated ALGS may accelerate hepatic deterioration [ 3 , 5 ] . Our case, demonstrating genuine coexistence of both entities, therefore represents a unique clinical scenario that compelled surgical intervention despite the ALGS diagnosis. The coexistence of these two distinct hepatopathies in a single patient suggests the possibility of under-recognized pathophysiological intersections. It prompts consideration of whether there might be shared genetic susceptibilities or interacting molecular pathways that predispose a subset of infants with ALGS to develop a concomitant, destructive cholangiopathy resembling BA. This case provides clinical clues that warrant further investigation into potential synergistic mechanisms. From a clinical perspective, this report underscores critical lessons. In infants presenting with cholestasis, a high index of suspicion for ALGS is imperative, particularly in the presence of suggestive facial features or a positive family history. Early genetic testing can provide definitive diagnosis and guide appropriate management. Crucially, for infants with a confirmed diagnosis of BA—even in the context of concomitant ALGS—our experience suggests that proceeding with early Kasai surgery remains a viable and potentially beneficial approach to modify disease progression, contrary to concerns raised in cases of misdiagnosed ALGS alone. Conclusions In summary, we document the first confirmed case of ALGS and BA coexistence. This unique scenario highlights the importance of comprehensive evaluation in complex cholestasis and expands our differential diagnostic reasoning. It further provides a clinical foundation for future research into potential common pathogenic pathways between these two distinct disorders. As a single case report with intermediate-term follow-up, the long-term prognosis for this rare comorbidity requires further observation. The generalizability of the treatment approach and its outcomes need validation through larger, multi-center studies and longer follow-up periods. Declarations Clinical trial number: not applicable. Acknowledgements Thank you to the medical writer, proofreader, and editor for their assistance with this article. Ethics approval and consent to participate Research study protocols were approved by the Ethics Committee of the School of Medicine, Xiamen University. Parents provided written informed consent to participate and the pediatric patient provided assent. Consent Written informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests I have no competing interests Data availability statement No datasets were generated or analysed during the current study. Author Contributions Corresponding author：Guoxian Huang 1 , Management and coordination responsibility for the research activity planning and execution. It is critical commentary, review, or revision, including pre - or post publication stages. Email： [email protected] Lead author：Si Li 1 , Preparation, creation, especially writing initial drafts (including substantive translation). Second author：Xiangde Lin 1 , Preparation, creation, especially writing initial drafts (including substantive translation). Third author：Lili Ma 1 , It is critical commentary, review, or revision, including pre - or post publication stages. Fourth author：Xin Lei 1 , It is critical commentary, review, or revision, including pre - or post publication stages. Fifth author：Tingting You 2 , Preparation, creation, especially writing initial drafts (including substantive translation). All authors reviewed the manuscript. Funding Declaration No funding was received to assist with the preparation of this manuscript. References BAIRD L C, SMITH E R, ICHORD R, et al. Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization [J]. J Pediatr. 2015;166(2):470–3. FERRARA G, GIANI T, LIEBERMAN SM, et al. Alagille Syndrome and Chronic Arthritis: An International Case Series [J]. J Pediatr. 2020;218:228–e301. VANDRIEL S M, LI L T, SHE H, et al. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study [J]. Hepatology (Baltimore MD). 2023;77(2):512–29. EMERICK K M, RAND E B GOLDMUNTZE, et al. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis [J]. Hepatology (Baltimore MD). 1999;29(3):822–9. EASL Clinical Practice Guidelines on. genetic cholestatic liver diseases [J]. J Hepatol. 2024;81(2):303–25. Additional Declarations No competing interests reported. Supplementary Files 1.jpg facial feature 2.jpg Laparoscopic imaging of the liver and gallbladder 3.jpg A: Partial liver tissue: A small amount of liver tissue was sent for examination, hepatocyte swelling and cholestasis, and small bile duct hyperplasia in the duct area was accompanied by fibrous tissue hyperplasia and lymphocyte infiltration, which was consistent with liver cholestasis (stage G2S2). B: Hepatic hilar fiber block and gallbladder: Local stenosis, discontinuous bile duct tissue with chronic inflammation infiltration Cite Share Download PDF Status: Published Journal Publication published 27 Dec, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 03 Dec, 2025 Reviews received at journal 03 Dec, 2025 Reviewers agreed at journal 02 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviews received at journal 01 Dec, 2025 Reviewers agreed at journal 27 Nov, 2025 Reviewers agreed at journal 27 Nov, 2025 Reviewers invited by journal 26 Nov, 2025 Editor invited by journal 21 Nov, 2025 Editor assigned by journal 21 Nov, 2025 Submission checks completed at journal 21 Nov, 2025 First submitted to journal 16 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8128374","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":551984806,"identity":"89b1d367-be20-472a-b980-5dc47651ed4d","order_by":0,"name":"Si Li","email":"","orcid":"","institution":"Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Si","middleName":"","lastName":"Li","suffix":""},{"id":551984807,"identity":"c54d5f3a-d52f-4fcf-8be5-2b2fa1e62070","order_by":1,"name":"Xiangde Lin","email":"","orcid":"","institution":"Xiamen 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21:29:52","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":39052,"visible":true,"origin":"","legend":"\u003cp\u003efacial feature\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8128374/v1/0288585552cc7152fc5203ec.jpg"},{"id":97665414,"identity":"4d84c77c-55a2-4f7c-b2b9-91e1f62004e5","added_by":"auto","created_at":"2025-12-08 09:18:15","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":66314,"visible":true,"origin":"","legend":"\u003cp\u003eLaparoscopic imaging of the liver and gallbladder\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8128374/v1/5c9cde1dc1fd5b1667a42649.jpg"},{"id":97665229,"identity":"160071e7-b6c5-464c-b693-2baa9b2327d4","added_by":"auto","created_at":"2025-12-08 09:17:29","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":119344,"visible":true,"origin":"","legend":"\u003cp\u003eA: Partial liver tissue: A small amount of liver tissue was sent for examination, hepatocyte swelling and cholestasis, and small bile duct hyperplasia in the duct area was accompanied by fibrous tissue hyperplasia and lymphocyte infiltration, which was consistent with liver cholestasis (stage G2S2). B: Hepatic hilar fiber block and gallbladder: Local stenosis, discontinuous bile duct tissue with chronic inflammation infiltration\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8128374/v1/8cabc21014e01efcd0f17e64.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Coexistence of Alagille Syndrome and Biliary Atresia in a Neonate: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eAlagille syndrome (ALGS) is an autosomal dominant multisystem disorder caused by pathogenic variants in JAG1 or NOTCH2, core components of the Notch signaling pathway\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In contrast, biliary atresia (BA) is an idiopathic, progressive cholangiopathy of infancy characterized by obliteration of the extrahepatic bile ducts\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Although both disorders present with cholestasis in infancy, their underlying pathogenesis, anatomical defects, and management strategies are fundamentally distinct.\u003c/p\u003e\u003cp\u003eNotably, the phenotypic overlap can lead to misdiagnosis. Instances of ALGS being mistaken for BA have been reported, with one study suggesting that Kasai portoenterostomy may accelerate liver dysfunction in ALGS patients\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, the true coexistence of both ALGS and BA in a single neonate has not been previously documented. Given their distinct pathogenic mechanisms and treatment approaches, accurate differentiation between these two entities is crucial. Herein, we report a unique case of concurrent ALGS and BA in a neonate, detailing the clinical presentation, diagnostic workup, and therapeutic management, with the aim of enhancing clinical recognition and guiding optimal management in such complex scenarios.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 1-month-old infant was admitted with persistent jaundice, clay-colored stools, and abdominal distension. Physical examination revealed moderate icteric sclerae and skin, along with distinctive facial features including a broad forehead, deep-set eyes with hypertelorism, a straight nasal bridge, a pointed chin, and a characteristic triangular facies (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Abdominal examination showed distension with the liver palpable 2.5 cm below the right costal margin.\u003c/p\u003e\u003cp\u003eLaboratory investigations demonstrated significant conjugated hyperbilirubinemia: total bilirubin 123.8 µmol/L, direct bilirubin 96.3 µmol/L. Liver enzymes were markedly elevated with ALT 451.8 U/L, AST 409.2 U/L, GGT 766.0 U/L, and ALP 456.3 U/L. Serum matrix metalloproteinase-7 (MMP-7) was elevated at 118.74 ng/ml. Genetic testing identified a heterozygous pathogenic variant in the JAG1 gene, consistent with Alagille syndrome type 1. Familial genetic screening revealed the same heterozygous JAG1 mutation in the father, while the mother showed no abnormalities.\u003c/p\u003e\u003cp\u003eAbdominal ultrasound with shear wave elastography showed hepatomegaly (liver extending 2.4 cm below right costal margin) with increased parenchymal echogenicity and echo enhancement of the Greenson sheath. The gallbladder and common bile duct were not visualized.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAfter 3 weeks of treatment with glutathione, diammonium glycyrrhizate and ursodeoxycholic acid, the jaundice showed minimal improvement, and the stools remained acholic. Laparoscopic exploration revealed a mildly enlarged liver with a dark color and tough texture. Spider nevus-like capillary dilatation was observed on the surface of the liver, and a striated gallbladder measuring approximately 1.0 cm × 0.3 cm was identified (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The gallbladder fundus was incised, revealing a solid, non-lumenal structure, so the cholangiogram was not possible. Intraoperative diagnosis: 1. BA; 2. ALGS. Following the Kasai portoenterostomy, the postoperative regimen comprised cefoperazone, sulbactam, glutathione, glycyrrhizinate, ursodeoxycholic acid, methylprednisolone, intravenous fluid and high nutritional status support. After the operation, the yellow skin and sclera of the child disappeared significantly, and the stool turned yellow. Postoperative pathological findings were consistent with cholestasis and BA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). After 8 months of follow-up, there was no yellow staining on the skin or sclera, and the color of the stool is normal. Biochemical and ultrasound examinations have not shown any significant abnormalities.\u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eWe herein report a rare case of ALGS associated with BA in infancy and explains the diagnosis, treatment process and follow-up prognosis of this case in detail. This study provides clues for the potential and under-recognized pathophysiological intersections or synergistic pathogenic mechanisms of ALGS and BA, broadens the differential diagnostic thinking in children with complex cholestasis, and provides new research ideas for in-depth exploration of whether ALGS and BA have common or mutually affecting genetic susceptibility, molecular pathways, and pathogenesis.\u003c/p\u003e\u003cp\u003eThe pathogenic mechanisms underlying ALGS and BA are fundamentally distinct. ALGS is directly attributable to pathogenic variants in JAG1 or NOTCH2, leading to multisystem involvement. In contrast, the etiology of BA remains elusive, potentially involving viral triggers, immune dysregulation, or environmental factors in a multifactorial model. Anatomically, ALGS is characterized by intrahepatic bile duct paucity, whereas BA presents with a complete obliteration of the extrahepatic biliary tree. This anatomical distinction underpins their divergent management strategies: BA necessitates prompt surgical intervention like the Kasai procedure to restore bile flow, while management of ALGS is primarily supportive, with liver transplantation reserved for end-stage liver disease. Notably, previous reports have indicated that performing Kasai portoenterostomy in patients misdiagnosed with BA but later confirmed to have isolated ALGS may accelerate hepatic deterioration\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Our case, demonstrating genuine coexistence of both entities, therefore represents a unique clinical scenario that compelled surgical intervention despite the ALGS diagnosis.\u003c/p\u003e\u003cp\u003eThe coexistence of these two distinct hepatopathies in a single patient suggests the possibility of under-recognized pathophysiological intersections. It prompts consideration of whether there might be shared genetic susceptibilities or interacting molecular pathways that predispose a subset of infants with ALGS to develop a concomitant, destructive cholangiopathy resembling BA. This case provides clinical clues that warrant further investigation into potential synergistic mechanisms.\u003c/p\u003e\u003cp\u003eFrom a clinical perspective, this report underscores critical lessons. In infants presenting with cholestasis, a high index of suspicion for ALGS is imperative, particularly in the presence of suggestive facial features or a positive family history. Early genetic testing can provide definitive diagnosis and guide appropriate management. Crucially, for infants with a confirmed diagnosis of BA—even in the context of concomitant ALGS—our experience suggests that proceeding with early Kasai surgery remains a viable and potentially beneficial approach to modify disease progression, contrary to concerns raised in cases of misdiagnosed ALGS alone.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, we document the first confirmed case of ALGS and BA coexistence. This unique scenario highlights the importance of comprehensive evaluation in complex cholestasis and expands our differential diagnostic reasoning. It further provides a clinical foundation for future research into potential common pathogenic pathways between these two distinct disorders. As a single case report with intermediate-term follow-up, the long-term prognosis for this rare comorbidity requires further observation. The generalizability of the treatment approach and its outcomes need validation through larger, multi-center studies and longer follow-up periods.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThank you to the medical writer, proofreader, and editor for their assistance with this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch study protocols were approved by the Ethics Committee of the School of Medicine, Xiamen University. Parents provided written informed consent to participate and the pediatric patient provided assent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI have no\u0026nbsp;competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorresponding author：Guoxian Huang\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e , Management and coordination responsibility for the research activity planning and execution. It is critical commentary, review, or revision, including pre - or post publication stages. Email：[email protected]\u003c/p\u003e\n\u003cp\u003eLead author：Si Li\u003csup\u003e1\u0026nbsp;\u003c/sup\u003e, Preparation, creation, especially writing initial drafts (including substantive translation).\u003c/p\u003e\n\u003cp\u003eSecond author：Xiangde Lin\u003csup\u003e1\u003c/sup\u003e , Preparation, creation, especially writing initial drafts (including substantive translation).\u003c/p\u003e\n\u003cp\u003eThird author：Lili Ma\u003csup\u003e1\u003c/sup\u003e , It is critical commentary, review, or revision, including pre - or post publication stages.\u003c/p\u003e\n\u003cp\u003eFourth author：Xin Lei\u003csup\u003e1\u003c/sup\u003e, It is critical commentary, review, or revision, including pre - or post publication stages.\u003c/p\u003e\n\u003cp\u003eFifth author：Tingting You\u003csup\u003e2\u003c/sup\u003e, Preparation, creation, especially writing initial drafts (including substantive translation).\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBAIRD L C, SMITH E R, ICHORD R, et al. Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization [J]. J Pediatr. 2015;166(2):470\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFERRARA G, GIANI T, LIEBERMAN SM, et al. Alagille Syndrome and Chronic Arthritis: An International Case Series [J]. J Pediatr. 2020;218:228\u0026ndash;e301.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVANDRIEL S M, LI L T, SHE H, et al. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study [J]. Hepatology (Baltimore MD). 2023;77(2):512\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEMERICK K M, RAND E B GOLDMUNTZE, et al. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis [J]. Hepatology (Baltimore MD). 1999;29(3):822\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEASL Clinical Practice Guidelines on. genetic cholestatic liver diseases [J]. J Hepatol. 2024;81(2):303\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Alagille Syndrome, Biliary Atresia, neonate","lastPublishedDoi":"10.21203/rs.3.rs-8128374/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8128374/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAlagille syndrome (ALGS) is an autosomal dominant disorder caused by gene mutations. Although its cholestatic manifestations may resemble those of biliary atresia (BA), the two conditions are distinct disease entities with fundamentally different pathogenesis, diagnostic approaches, and management strategies.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e\u003cp\u003eWe report a case of a female Han Chinese neonate with BA concomitant with ALGS. The diagnosis of ALGS was confirmed based on clinical manifestations and genetic testing findings. After conservative treatment failed to show improvement, operative exploration confirmed BA. The neonate underwent Kasai portoenterostomy and achieved successful recovery. Post-operative follow-up for over eight months has exhibited a favorable prognosis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis is the first report of BA and ALGS co-existence. The concurrent presence of these two distinct hepatopathies creates significant diagnostic pitfalls, highlighting the imperative for heightened clinical vigilance to prevent misdiagnosis, delayed interventions, and inappropriate treatment.\u003c/p\u003e","manuscriptTitle":"Coexistence of Alagille Syndrome and Biliary Atresia in a Neonate: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-03 21:29:47","doi":"10.21203/rs.3.rs-8128374/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-04T04:53:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T07:51:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294041984166883809608262341978462001680","date":"2025-12-02T11:02:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93936912238423554993966521791261002412","date":"2025-12-02T04:39:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-01T12:20:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301577588179175768976454909056724452004","date":"2025-11-28T01:20:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87261079111995697091229560233965338203","date":"2025-11-27T05:18:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-27T04:13:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-21T09:54:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-21T07:45:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-21T07:45:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-11-16T16:06:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8ea7853c-fb47-404e-b528-5c829e6d1531","owner":[],"postedDate":"December 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:06:40+00:00","versionOfRecord":{"articleIdentity":"rs-8128374","link":"https://doi.org/10.1186/s12887-025-06467-x","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-12-27 15:58:31","publishedOnDateReadable":"December 27th, 2025"},"versionCreatedAt":"2025-12-03 21:29:47","video":"","vorDoi":"10.1186/s12887-025-06467-x","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06467-x","workflowStages":[]},"version":"v1","identity":"rs-8128374","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8128374","identity":"rs-8128374","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}