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 benign course in these patients. Subsequent reports showed significant morbidity and mortality. This study was designed to analyze the long-term clinical course in Alagille syndrome.
METHODS: The records of children with Alagille syndrome seen during a 20-year 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%) and intracranial hemorrhage (12%) were significant. The high incidence of chronic otitis media (35%) has not been reported previously. One patient had a renal transplant. Vascular compromise as a pathologic mechanism for some characteristics of the syndrome is also suggested by the presence of small bowel stenosis and atresia, tracheal and bronchial stenosis, renal artery stenosis, middle aortic syndrome, and avascular necrosis of the humeral and femoral heads. Twenty (47%) patients underwent liver transplantation. Five of six who underwent Kasai procedure required liver transplantation. Twelve died (28%), five after liver transplantation. One patient died of intracranial 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 can benefit from liver transplantation. Careful and complete assessment should be made of infants with a cholestatic syndrome, to avoid misdiagnosis and unnecessary Kasai procedures. Our observation of vascular compromise in various organ systems suggests that notch signaling pathway defects affect angiogenesis in Alagille syndrome.