Genotypic and phenotypic profiles of children in China with Alagille syndrome (ALGS) suggest regional variability and calling for better screening methods, according to a study recently published as a preprint in Research Square.

“Through the study, we have realized that the primary pediatricians’ cognition of ALGS is insufficient, which is why we wrote this manuscript,” the authors said.

This retrospective research analyzed clinical data from 10 children previously diagnosed with ALGS, including 8 males and 2 females from 1 month to 6 years old, with a median age of 2.5 months.

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Most of them (80%) presented with cholestasis, commonly in the first 3 months of age, which led them to hospitalization, and diagnostic tests that eventually determined ALGS as the causal disease. Regardless, many also had abnormalities in multiple organs and systems.

For example, liver and heart showcased some degree of impairment in 100% of cases, followed by facial abnormalities in 70%, while 40% had skeleton deformities and/or low weight below the third percentile for age, 30% had kidney involvement, and 10% had experienced an epileptic seizure, suggesting brain involvement.

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Regarding laboratory findings, the median total and direct bilirubin, as well as total bile acid in the blood, were well above the normal range, often surpassing it by 100 mmol/L. Gamma-glutamyl transpeptidase mean value was also elevated at 223 U/L for a normal range of 9-64 U/L, and 60% of the participants also had increased cholesterol values.

Liver biopsy reported ductular proliferation in 1 case and intrahepatic bile duct paucity with giant cell hepatitis in another patient. No other participants underwent a liver biopsy, which corresponds with current guidelines that advise against it as part of the routine workup for ALGS.

Genetic testing revealed 9 patients had 8 different mutations in the JAG1 gene, including 5 nonsense, 3 frameshifts, and 1 splicing variant. Lastly, 1 nonsense mutation in the NOTCH2 gene accounted for the remaining case. Notably, most of these genotypes have not yet been reported in the literature, assuming a regional variability characteristic of China. This may also explain the unexpected finding that no patient presented with ocular abnormalities.

“First, posterior embryotoxon is so rare that our ophthalmologists could not identify it accurately; second, we hypothesize that this may be a feature of the Chinese children with ALGS,” the authors concluded.


Chen Y, Sun M, Teng X. Clinical and genetic analysis in Chinese children with Alagille syndrome. Res Sq. Published online July 6, 2022. doi:10.21203/