Key indicators and genetic testing crucial for early diagnosis of Alagille syndrome in children

Early and accurate diagnosis of Alagille syndrome (ALGS) in children can be improved by focusing on the presence of cholestasis and using genetic testing, particularly for mutations in the JAG1 gene., according to a study This approach helps reduce the risk of misdiagnosis and guides effective treatment, including considering liver transplantation in severe cases.

The study retrospectively reviewed data from 17 children diagnosed with ALGS between January 2012 and January 2022. The researchers examined clinical symptoms, liver pathology, and genetic testing results to better understand the syndrome.

The study found that most of the children (94%) exhibited cholestasis, a condition where bile flow is reduced or blocked. Other common features included characteristic facial features (88%), heart disease (75%), butterfly-shaped vertebrae (71%), and posterior embryotoxon (58%). Liver pathology revealed bile duct paucity in 87% of the patients who underwent liver biopsies. Genetic testing identified mutations in the JAG1 gene in 13 of the 15 tested children, with four novel variants discovered. No mutations in the NOTCH2 gene were found.

The study concluded that children showing signs of cholestasis should undergo genetic testing and be evaluated using the revised diagnostic criteria for ALGS to avoid misdiagnosis.

Reference
Yan J, Huang Y, Cao L, et al. Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome. BMC Pediatr. 2024;24(1):532. doi: 10.1186/s12887-024-04973-y. PMID: 39164659; PMCID: PMC11334458.