ABSTRACT
We have studied 92 patients with Alagille syndrome (AGS) to determine the frequency of clinical manifestations and to correlate the clinical findings with outcome. Liver biopsy specimens showed paucity of the interlobular ducts in 85% of patients. Cholestasis was seen in 96%, cardiac murmur in 97%, butterfly vertebrae in 51%, posterior embryotoxon in 78%, and characteristic facies in 96% of patients. Renal disease was present in 40% and intracranial bleeding or stroke occurred in 14% of patients. The presence of intracardiac congenital heart disease was the only clinical feature statistically associated with increased mortality (P <.001). Initial measures of hepatic function in infancy including absence of scintiscan excretion were not predictive of risk for transplantation or increased mortality. The hepatic histology of these AGS patients showed a significant increase in the prevalence of bile duct paucity (P =.002) and fibrosis (P <.001) with increasing age. Liver transplantation for hepatic decompensation was necessary in 21% (19 of 92) of patients with 79% survival 1-year posttransplantation. Current mortality is 17% (16 of 92). The factors that contributed significantly to mortality were complex congenital heart disease (15%), intracranial bleeding (25%), and hepatic disease or hepatic transplantation (25%). The 20-year predicted life expectancy is 75% for all patients, 80% for those not requiring liver transplantation, and 60% for those who required liver transplantation.
Subject(s)
Alagille Syndrome/complications , Adolescent , Adult , Alagille Syndrome/diagnosis , Alagille Syndrome/surgery , Bone Diseases/etiology , Cardiovascular Diseases/etiology , Cerebral Hemorrhage/etiology , Child , Child, Preschool , Cholestasis/etiology , Developmental Disabilities/etiology , Digestive System/diagnostic imaging , Eye Diseases/etiology , Growth Disorders/etiology , Humans , Infant , Kidney Diseases/etiology , Liver/pathology , Liver Transplantation , Prognosis , Radiography , Radionuclide ImagingABSTRACT
OBJECTIVES: To describe the patterns of growth, nutritional status, body composition, and resting energy expenditure (REE) in prepubertal children with Alagille syndrome (AGS) before the onset of end-stage liver disease. STUDY DESIGN: Thirteen prepubertal subjects with AGS (8 male; mean age, 6.8 2.8 years) were evaluated for growth parameters, body composition by skinfolds and by dual-energy x-ray absorptiometry, and REE by indirect calorimetry. The children with AGS were compared with a healthy, age-matched reference group of 37 prepubertal children. RESULTS: Compared with healthy children, children with AGS had significantly reduced (P <. 05) growth (weight, weight z score, height, height z score), nutritional status (midarm circumference, triceps skinfold, and midarm muscle area), and body composition (fat mass and fat-free mass). Subscapular thickness, percent body fat, and REE were not different. The AGS subgroup (n = 4) with REE greater than 110% predicted value had a reduced percent body fat (P <.02). CONCLUSIONS: Growth and body composition abnormalities are common in prepubertal children with AGS.