LIVER CYTOCHROME-C-OXIDASE DEFICIENCY IN A CASE OF NEONATAL-ONSET HEPATIC-FAILURE

In the last few years, inborn errors of oxidative phosphorylation have been recognized as possible causes of hepatic failure in infancy and respiratory enzyme deficiencies have been described in several tissues of affected individuals. Here, we report on cytochrome c oxidase defi ciency in the Liver but not in the skeletal muscle of a 5-month-old gi rl who presented hepatic failure in early infancy. Persistent hyperlac tataemia (> 4 mM, normal < 2.4) with high lactate/pyruvate (L/P) molar ratios in plasma, and their further elevation in the post-absorptive period were suggestive of an inborn error of oxidative phosphorylation . However, no mutation in the coding sequences of the liver-specific s ubunits of cytochrome c oxidase (VIa and VIIa) has been detected and n o major rearrangement or depletion of the mitochondrial DNA has been o bserved. Based on this observation we suggest that inborn errors of ox idative phosphorylation be considered in the diagnosis of severe hepat ocellular dysfunction of unknown origin, especially when an abnormal o xidation-reduction status is found in the plasma and even if normal re spiratory enzyme activities are found in peripheral tissues. The findi ng of normal respiratory enzyme activities in skeletal muscle, circula ting lymphocytes or cultured skin fibroblasts does not rule out this d iagnosis. Instead, the negativity of these tests should prompt one to carry out the specific enzyme assays in the tissue which expresses the disease, namely the liver.