Alagille综合征(ALGS)是一种多系统疾病,具有可变的临床外显率。导致这种疾病的基因是JAGGED1(JAG1)和NOTCH2。这种疾病的临床资料在中国是有限的。本研究的目的是通过总结这些病例的临床特征和遗传变异,丰富中国儿童Alagille综合征的现有资料。从2011年1月到2022年2月,10名儿童被诊断为ALGS。ALGS涉及的器官如下:肝脏(10,100%);心脏(7,70%);特征性面部特征(7,70%);骨骼(4,40%);大脑(1,10%)和肾脏(3,30%)。四名患者(40%)小于胎龄。主要临床表现为胆汁淤积,心脏病,和面部特征。中位数总胆红素,直接胆红素,总胆汁酸水平为138.75μmol/L(正常,3.4-20.5μmol/L),107.25μmol/L(正常,0-8.6μmol/L),和110.65μmol/L(正常,0.5-10.0μmol/L),分别。γ-谷氨酰转肽酶的中位数为223U/L(正常,9-64U/L)。六个(60%)儿童患有高胆固醇血症。在10例中国ALGS患者中鉴定出8种不同的JAG1基因变异和1种NOTCH2基因致病变异。
胆汁淤积是中国ALGS患儿最常见的首发症状。JAG1和NOTCH2的致病变异体是中国ALGS患儿的主要突变,但我们有自己独特的变异谱.ALGS应考虑用于婴儿和幼儿的胆汁淤积,尤其是那些有多器官异常的人.
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.