Mitochondrial cytopathies are multisystemic disorders of extremely variable expression due to a deficiency in oxidative phosphorylation. Cases have recently been reported in which fatal liver failure with neonatal onset was the major clinical and biochemical syndrome. In this series we reviewed the liver histology of 10 such patients who died in the first weeks of life (from 3 days to 6 mo). In six cases the diagnosis was confirmed by study of the mitochondrial respiratory chain in the muscle, liver or both; in the other four, appropriate tests were not available for diagnosis but symptoms were identical and all other diagnoses were ruled out. In all 10 cases we noted significant steatosis, mostly microvesicular; widespread hepatocytic, canalicular and bile duct cholestasis with bile thrombi and cholangiolar proliferation; and different degrees of hepatosiderosis and glycogen depletion. Fibrosis took varying forms: perisinusoidal, periportal with the formation of septa, even precirrhosis. In the two cases of infants who died, one at 5 and one 6 mo, micronodular cirrhosis was also present. Mitochondria, either densely or loosely packed, were abnormal-pleiomorphic with few or no cristae and a granular fluffy matrix. Dense, large granules were seen in two cases. The association of neonatal liver failure and hyperlactacidemia should lead to immediate examination of the respiratory chain. The expression of this mitochondrial cytopathy can be lethal, associated with severe liver damage due to the deficiency in oxidative phosphorylation.

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Inborn errors of one or more of the complexes of the respiratory chain are increasingly being recognized as important causes of disease. Patients with these defects present in a variety of ways, including cases of fatal lactic acidosis in infancy. We describe here three cases of neonatal lactic acidosis in which the prominent features were hypertyrosinaemia and severe hepatic failure. They were shown to be the result of a defect in one or several complexes of the respiratory chain. Table 1. Mitochondria were isolated, when possible, from a muscle biopsy using the procedure of Morgan-Hughes and colleagues (1982). The respiratory activities are expressed in natom O rain-1 (rag protein)-1. The enzymatic assays were performed as described by Birch-Machin and colleagues (t989). The enzyme assays of fumaryl acetoacetase (FAA) were performed by Dr Berger (Groningen). PATIENTS AND METHODS AllA small part of the biopsy was also permeabilized in order to study respiratory parameters according to the methods of Veksler and colleagues (1987)