Severe complex I deficiency in a case of neonatal-onset lactic acidosis and fatal liver failure.

We report a newborn admitted to our service on the 2nd day of life because of hypotonia and metabolic acidosis. A progressive hepatocellular dysfunction dominated the clinical picture and the patient died at 13 months of age because of severe hepatic failure. Persistent lactic acidosis, high ketone bodies levels and high-normal lactate/pyruvate and 3-hydroxybutyrate/acetoacetate molar ratios in plasma were found. Investigation of a liver biopsy revealed low activities of all the mitochondrial respiratory chain enzymes but in particular a marked decrease of complex I (NADH cytochrome c reductase) activity. All respiratory chain enzyme activities were normal in cultured skin fibroblasts. Mitochondrial DNA analysis failed to detect any major rearrangements. Although only a few cases have been reported so far, it is becoming clear that liver should be considered as one of the organs involved in oxidative phosphorylation disorders. The finding of unexplained progressive liver failure with poor neurological conditions, lactic acidaemia and ketonuria strongly warrants investigation for a respiratory chain disorder. Moreover, the finding of normal respiratory enzyme activities in a tissue other than liver does not rule out the existence of an oxidative phosphorylation disorder in patients with hepatocellular disease of unexplained origin.