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 bec ause 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 ac idosis, high ketone bodies levels and high-normal lactate/pyruvate and 3-hydroxybutyrate/acetoacetate molar ratios in plasma were found. Inv estigation of a liver biopsy revealed low activities of all the mitoch ondrial respiratory chain enzymes but in particular a marked decrease of complex I (NADH cytochrome c reductase) activity. All respiratory c hain enzyme activities were normal in cultured skin fibroblasts. Mitoc hondrial DNA analysis failed to detect any major rearrangements. Altho ugh only a few cases have been reported so far, it is becoming clear t hat liver should be considered as one of the organs involved in oxidat ive phosphorylation disorders. The finding of unexplained progressive liver failure with poor neurological conditions, lactic acidaemia and ketonuria strongly warrants investigation for a respiratory chain diso rder. Moreover, the finding of normal respiratory enzyme activities in a tissue other than liver does not rule out the existence of an oxida tive phosphorylation disorder in patients with hepatocellular disease of unexplained origin.