Síndrome de Alagille na pediatria: estudo observacional retrospectivo em serviço de gastroenterologia e hepatologia pediátrica

Abstract

Alagille syndrome is a genetic disorder with autosomal dominant inheritance, characterized by chronic cholestasis associated with multisystem involvement and marked clinical and evolutionary heterogeneity in the pediatric population.Objective: To describe the clinical, laboratory, histological, genetic, therapeutic profile and outcomes of children and adolescents diagnosed with Alagille syndrome followed at a tertiary pediatric gastroenterology and hepatology center in Bahia, Brazil. Methods: This was a retrospective observational case series including patients aged 0 to 18 years with a clinical, histological and/or genetic diagnosis of Alagille syndrome. Demographic data, hepatic and extrahepatic clinical manifestations, laboratory findings at diagnosis and after approximately 12 months of follow-up, histological features, genetic testing results, treatments and clinical outcomes were analyzed. Results: Eleven patients were included, with a slight predominance of females. Persistent neonatal cholestasis and jaundice were present in all cases. Pruritus was observed in 63.6% of patients, with severe or intractable forms in some, frequently associated with dyslipidemia and xanthomas. Congenital heart disease was identified in 72.7% of individuals. Skeletal and ophthalmologic abnormalities, such as butterfly vertebrae and posterior embryotoxon, were also frequent findings. Liver biopsy revealed heterogeneous patterns, including ductopenia, ductular proliferation and cholestasis without ductopenia. Genetic testing identified variants in the JAG1 gene in a subset of patients. Discussion: Clinical management was mainly based on ursodeoxycholic acid and fat-soluble vitamin supplementation, with partial and heterogeneous laboratory response after approximately one year of follow-up. Conclusion: A variable clinical course was observed, with frequent dissociation between biochemical response and symptom control. Additionally, 45.5% of patients progressed to liver transplantation, highlighting the severity and unpredictable nature of Alagille syndrome.