MITOCHONDRIAL RESPIRATORY-CHAIN DEFECT - A NEW ETIOLOGY FOR NEONATAL CHOLESTASIS AND EARLY LIVER INSUFFICIENCY

Two siblings presented with neonatal cholestasis and early liver insuf ficiency. The older was admitted for end-stage cirrhosis with severe h ypoglycemia and had long-term successful liver transplant at the age o f 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work-up excluded all known causes of neonatal cholestasis, Gluconeogenesis was found normal following alani ne and fructose infusion. Repeated hypoglycemia with early post-prandi al hyperlactacidemia led us to investigate the mitochondrial respirato ry chain enzyme activities. Selective defects of complexes I, III and IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and on preserved frozen tissue from his sibling, whilst normal activities were found in liver tissue samples from control patients w ith end-stage liver diseases, No extrahepatic manifestations were foun d, We conclude that liver deficiency of mitochondrial respiratory chai n enzymes may cause liver disease in neonates, associated with hypogly cemia and post-prandial hyperlactacidemia, The disease is cured by liv er transplantation.