Prolonged survival in three brothers with severe type 2 Crigler-Najjar syndrome. Ultrastructural and metabolic studies

Abstract

Three brothers with severe type 2 Crigler-Najjar syndrome for over 50 years have been studied. Although the plasma unconjugated bilirubin (UCB) concentrations were in excess of 19 mg per 100 ml, no abnormal neurological signs were evident. Prolonged exposure to severe unconjugated hyperbilirubinemia does not therefore necessarily increase morbidity. Electron microscopy of liver tissue obtained from 2 patients before phenobarbital therapy showed hypertrophy and hyperplasia of smooth endoplasmic reticulum with unusual prominence of the Golgi apparatus and focal modification of the cell surface membranes. These changes may reflect the reactive state of the hepatocyte to high levels of unconjugated bilirubin. Phenobarbital therapy resulted in a marked reduction in UCB concentration and was accompanied by further hypertrophy of the smooth endoplasmic reticulum and minor changes in bile canaliculi. Dietary restriction to 400 cal daily for 3 days produced a dramatic increase in UCB. The addition of 2400 cal by the intravenous administration of 50% dextrose did not reduce the elevated UCB. In contrast, 2400 cal fed as a normal diet rapidly returned the UCB to basal levels. While on phenobarbital therapy, a similar response to caloric withdrawal and parenteral feeding was observed. These findings indicate that the hyperbilirubinemia of fasting does not depend on caloric deficiency per se, and suggest that either the route of caloric administration or the type of nutrient may influence the level of unconjugated hyperbilirubinemia.