[Clinical characteristics and follow-up in children with Alagille syndrome]

Objective: To investigate the clinical and genetic features and follow-up outcomes in children with Alagille syndrome (ALGS). Methods: A retrospective cohort study was conducted. Clinical data from 24 children diagnosed with ALGS treated at Capital Children's Medical Center, Capital Medical University, from January 2015 to January 2025 were collected and analyzed. Genetic variation characteristics were collected by comparing biochemical indicator changes in children who were followed up for over six months before and after treatment. Independent samples t-tests or rank-sum tests were used to compare continuous data between groups. The correlation between liver stiffness and bile acid levels was compared using Spearman correlation analysis. Results: Out of the 24 enrolled cases, ten were male. The occurrence rate during the neonatal phase accounted for 62.5% (15/24), while the occurrence rate before six months of age was 87.5% (21/24). The median age at the time of confirmed diagnosis was 16 months (26 days, 11 years). The common clinical manifestations were cholestasis, accounting for 87.5% (21/24); hepatomegaly, 75.0% (18/24); distinctive facial features, 70.8% (17/24); and butterfly-shaped vertebrae, 45.8% (11/24). Cardiovascular involvement accounted for 45.8% (11/24). Growth and development retardation was observed in 37.5% (9/24). The pruritus incidence rate at the time of definite diagnosis in pediatric patients was 54.2% (13/24). Among the five pediatric patients who underwent liver biopsy, three had the typical pathology of intrahepatic bile duct insufficiency. Genetic examinations were performed in all 24 cases. The JAG1 gene mutation was present in 22 cases, while the NOTCH2 gene mutation was present in two. Exon deletion was detected in one case, splicing variants in eight, frameshift variations in six, nonsense variations in three, and missense variations in six. Among ALGS cases, 21 patients survived following autologous liver transplantation and were followed up for at least six months. Aspartate aminotransferase, total bilirubin, direct bilirubin, γ-glutamyl transferase, triglycerides, and low-density lipoprotein cholesterol were significantly declined (P<0.05). Serum cholesterol levels were increased during follow-up compared to the disease onset phase and showed a progressive trend with prolonged disease duration. Liver stiffness values exhibited an annual upward trend and correlated positively with bile acid levels. Conclusion: Cholestasis, hepatomegaly, distinctive facial features, and the presentation of early-stage liver fibrosis are common clinical manifestations during the ALGS diagnosis in pediatric patients. Certain liver disease indicators may improve following treatment, resulting in a substantial reduction in bilirubin levels; however, hypercholesterolemia may develop.