Clinical and genetic analysis in Chinese children with Alagille syndrome

Alagille syndrome (ALGS) is a multisystem disorder with variable clinical penetrance. The genes responsible for this disease are JAGGED1 (JAG1) and NOTCH2. Clinical data of this disease are limited in China. The purpose of this study was to enrich the present data of Chinese children with Alagille syndrome by summarizing the clinical characteristics and genetic variations of these cases. From January 2011 to February 2022, 10 children were diagnosed with ALGS. The organs involved in ALGS were as follows: liver (10, 100%); heart (7, 70%); characteristic facial features (7, 70%); skeleton (4, 40%); brain (1,10%) and kidney (3, 30%). Four patients (40%) were small for gestational age. The main clinical manifestations were cholestasis, heart disease, and facial features. The median total bilirubin, direct bilirubin, and total bile acid levels were 138.75 μmol/L (normal, 3.4-20.5 μmol/L), 107.25 μmol/L (normal, 0-8.6 μmol/L), and 110.65 μmol/L (normal, 0.5-10.0 μmol/L), respectively. The median value of gamma-glutamyltranspeptidase was 223 U/L (normal, 9-64 U/L). Six (60%) children had hypercholesteremia. Eight different JAG1 gene variations and one NOTCH2 gene pathogenic variant in the 10 Chinese ALGS patients were identified.

Cholestasis was the most common initial presenting symptom in Chinese ALGS pediatric patients. Pathogenic variants in JAG1 and NOTCH2 are the primary mutations in Chinese children with ALGS, but we had our own unique variant spectrum. ALGS should be considered for cholestasis in infants and young children, especially those with multiorgan abnormalities.