Variable morbidity in Alagille syndrome: A review of 43 cases

Background: Alagille syndrome is one of the most common inherited disorders that cause chronic liver disease in children. Early reports suggested a be nign course in these patients. Subsequent reports showed significant morbid ity and mortality. This study was designed to analyze the long-term clinica l course in Alagille syndrome, Methods: The records of children with Alagille syndrome seen during a 20-ye ar period were reviewed. Results: Forty-three patients were identified. Liver disease was diagnosed before 12 months of age in 95%. The frequencies of renal anomalies (50%) an d intracranial hemorrhage (12%) were significant. The high incidence of chr onic otitis media (35%) has not been reported previously. One patient had a renal transplant. Vascular compromise as a pathologic mechanism for some c haracteristics of the syndrome is also suggested by the presence of small b owel stenosis and atresia, tracheal and bronchial stenosis, renal artery st enosis, middle aortic syndrome, and avascular necrosis of the humeral and f emoral heads. Twenty (47%) patients underwent liver transplantation. Five o f six who underwent Kasai procedure required liver transplantation. Twelve died (28%), five after liver transplantation. One patient died of intracran ial bleeding. Sixteen (37%) without liver transplantation and 15 (35%) who underwent liver transplantation are alive. Conclusions: Some patients with early-onset and more severe liver disease c an benefit from liver transplantation. Careful and complete assessment shou ld be made of infants with a cholestatic syndrome, to avoid misdiagnosis an d unnecessary Kasai procedures. Our observation of vascular compromise in v arious organ systems suggests that notch signaling pathway defects affect a ngiogenesis in Alagille syndrome.