From chronic cholestasis to liver transplantation

Introduction. Alagille Syndrome is a genetic autosomal dominant disorder with multisystemic manifestations. The diagnosis is suspected in children presenting with jaundice in the first 6 months of life (70%) with or without associated cardiac murmur (17%). Case presentation. We report the case of a 2 years and 2 months old boy who was first evaluated in our department at 3 days of age for jaundice and meconium ileus. Clinical examination showed abdominal distension and cardiac murmur. Laboratory tests revealed high levels of total and conjugated bilirubin, but normal transaminases, serum proteins and blood coagulation markers. Infectious causes were ruled out – HIV, HBV, HCV, EBV, CMV and syphilis. Echocardiography described large pulmonic stenosis with no hemodynamic implications. Thoraco-lumbar X-ray revealed no anomalies of the spine. Cystic Fibrosis was excluded. Alagille Syndrome was at that point the main diagnostic suspicion, but liver biopsy failed to reveal paucity of bile ducts. Further evaluation was conducted and ophthalmologic examination revealed posterior embryotoxon, one of the classic phenotypic traits of Alagille syndrome. Abdominal CT showed a nodular area in the IVth segment of the liver with no visualization of the bile duct and MRCP showed thin but present intra/extrahepatic biliary ducts and absence of the gallbladder. Genetic testing was not available at the time, but further on it confirmed the diagnosis of Alagille syndrome. The patient associated failure to thrive and signs of chronic cholestasis: severe jaundice, refractory pruritus, acholic stools, hepatosplenomegaly, xanthelasma, persistent hepatic cytolysis, severe dyslipidemia. Due to progressive, chronic hepato-biliary disease and advancing cirrhosis liver transplantation was considered and the patient was referred to a liver transplant facility in Palermo. Conclusions. Alagille syndrome is not always an easy diagnosis. In certain cases it takes time to reach it and set the course for an optimal therapeutic approach.