FATAL NEONATAL LIVER-FAILURE AND MITOCHONDRIAL CYTOPATHY (OXIDATIVE-PHOSPHORYLATION DEFICIENCY) - A LIGHT AND ELECTRON-MICROSCOPIC STUDY OFTHE LIVER

Mitochondrial cytopathies are multisystemic disorders of extremely var iable expression due to a deficiency in oxidative phosphorylation. Cas es have recently been reported in which fatal liver failure with neona tal onset was the major clinical and biochemical syndrome. In this ser ies we reviewed the liver histology of 10 such patients who died in th e first weeks of life (from 3 days to 6 mo). In six cases the diagnosi s 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 diag noses were ruled out. In all 10 cases we noted significant steatosis, mostly microvesicular: wide-spread hepatocytic, canalicular and bile d uct 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 s epta, 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 wer e seen in two cases. The association of neonatal liver failure and hyp erlactacidemia 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.