Alagille Syndrome – The Difficulty of Initial Diagnosis

Background: Alagille syndrome is a rare autosomal dominant disorder with systemic manifestations: paucity of the bile ducts, abnormalities of the heart, eye, skeleton and kidneys. It is diagnosed in children presenting with jaundice in the first 6 months of life (70%) or cardiac murmur (17%).

Objective: This case presentation emphasises the challenges faced in terms of diagnosis and therapy for one of these patients.

Method and Results: We report the case of a 3 days old boy admitted in the Paediatrics Department of “Grigore Alexandrescu” Children’s Hospital, Bucharest for bilious vomiting and intense jaundice. The newborn hadn’t pass the meconium. Clinical examination showed abdominal distension and cardiac murmur. Laboratory tests revealed high levels of conjugated bilirubin, normal transaminases, serum proteins and blood coagulation. Viral serologies were all negative. Thoraco-lumbar X-ray of the spine didn’t reveal any anomalies. Echocardiography described large pulmonary stenosis. Barium enema failed to pass meconium, exploratory laparotomy was performed for deobstruction. Cystic fibrosis was excluded. Alagille syndrome was the main diagnostic considered, but liver biopsy failed to reveal paucity of the bile ducts. Over the next two years the pacient underwent extensive investigations. A posterior embryotoxon was described. Abdominal CT could not visualise the bile duct. Abdominal MRI + cholangio-MRI showed thin intra/extrahepatic biliary ducts, cirrhotic nodules, the gallblader was not visible. Genetic testing was not available. The pacient associated failure to thrive. Signs of chronic disease began to surface in time: severe jaundice, hepatosplenomegaly, abdominal collateral circulation, persistent hepatic cytolysis and cholestasis, dyslipidemia. Due to progressive chronic hepato-biliary disease and advancing cirrhosis in a 2 years old with failure to thrive, liver transplant is now considered.

Conclusion: Although Alagille should be a straight forward diagnosis, in certain instances it takes time and sustained efforts to reach it and set the course for an optimal therapeutic approach.