To differentiate Alagille syndrome from other causes of cholestasis in children, focus on its distinctive clinical, biochemical, radiological, and genetic features. Alagille syndrome typically presents with cholestasis due to paucity of intrahepatic bile ducts, but unlike other cholestatic conditions, it is a multisystem disorder characterized by a combination of liver, cardiac, skeletal, ocular, and facial abnormalities NICE NG49 Gilbert & Loomes 2021.
Key clinical features include: a characteristic facial appearance (broad forehead, deep-set eyes, pointed chin), peripheral pulmonary artery stenosis or other congenital heart defects, butterfly vertebrae on spinal X-rays, and posterior embryotoxon in the eyes NICE NG49 Gilbert & Loomes 2021. These features help distinguish it from isolated biliary atresia or other metabolic causes of cholestasis.
Biochemically, children with Alagille syndrome often have elevated serum bile acids and conjugated hyperbilirubinemia, but gamma-glutamyl transferase (GGT) levels are typically normal or mildly elevated, which contrasts with other cholestatic diseases where GGT may be markedly raised NICE NG49 Wehrman & Lee 2022.
Histologically, liver biopsy shows paucity of intrahepatic bile ducts, a hallmark of Alagille syndrome, whereas other causes of cholestasis may show bile duct proliferation or obstruction NICE NG49 Gilbert & Loomes 2021.
Genetic testing for mutations in the JAG1 or NOTCH2 genes confirms the diagnosis and differentiates Alagille syndrome from other genetic or metabolic cholestatic disorders NICE NG49 Gilbert & Loomes 2021Wehrman & Lee 2022.
In summary, the diagnosis of Alagille syndrome is supported by the presence of multisystem clinical features, characteristic biochemical profile, bile duct paucity on liver biopsy, and confirmatory genetic testing, which together differentiate it from other causes of cholestasis in children NICE NG49 Gilbert & Loomes 2021Wehrman & Lee 2022Eiamkulbutr et al. 2024.
Key References
- NG49 - Non-alcoholic fatty liver disease (NAFLD): assessment and management
- CG71 - Familial hypercholesterolaemia: identification and management
- NG12 - Suspected cancer: recognition and referral
- (Gilbert and Loomes, 2021): Alagille syndrome and non-syndromic paucity of the intrahepatic bile ducts.
- (Wehrman and Lee, 2022): The cholestatic infant: updates on diagnosis and genetics.
- (Eiamkulbutr et al., 2024): Diseases of bile duct in children.