title: Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis and early liver insufficiency.
abstract: Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 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 alanine and fructose infusion. Repeated hypoglycemia with early post-prandial hyperlactacidemia led us to investigate the mitochondrial respiratory 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 with end-stage liver diseases. No extrahepatic manifestations were found. We conclude that liver deficiency of mitochondrial respiratory chain enzymes may cause liver disease in neonates, associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is cured by liver transplantation.
authors.affiliation: Service de Pédiatrie, Cliniques St Luc-Université Catholique de Louvain, Bruxelles, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Goncalves
authors.forename: D
authors.initials: D
authors.lastname: Hermans
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: F
authors.initials: F
authors.lastname: Van Hoof
authors.forename: R
authors.initials: R
authors.lastname: Reding
authors.forename: J
authors.initials: J
authors.lastname: de Ville de Goyet
authors.forename: J B
authors.initials: JB
authors.lastname: Otte
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000378:metabolism; D002779:Cholestasis / Q000150:complications / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000032:analysis; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000378:metabolism; D007223:Infant; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism*; D017093:Liver Failure / Q000209:etiology* / Q000378:metabolism / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D009679:Nuclear Family
chemical_list: D004272:DNA, Mitochondrial