Features of cell death in brain and liver, the target tissues of progressive neuronal degeneration of childhood with liver disease ( XXXX ).

@entity1 @entity410 @entity82 @entity522 @entity39 @entity75 @entity16 @entity409 @entity1092 @entity8187 @entity29409 @entity4519 @entity99 @entity528
@entity29409 ( @entity29409 ) is a rare @entity75 of infancy and childhood characterized by @entity410 and progressive @entity16 , usually associated with signs and symptoms of @entity409 . There is no biological marker of the disease, and ultimate diagnosis still relies on pathological examination. Features of clinical progression and pathological findings suggest @entity29409 to be secondary to a genetically determined disorder of mitochondrial function. We report on four @entity29409 @entity1 and focus on their pathological features in brain, liver and muscle. Liver and muscle biopsy specimens were examined using histochemical markers of the oxidative pathways, probes to immunodetect molecules of the apoptotic cascades and electron microscopy. In liver (but not in muscle) biopsy samples, activated caspases were detected by immunohistochemistry: foci of @entity8187 -positive cells were seen in a @entity1 affected with chronic, progressive @entity82 . In an 18-year-old @entity1 , who suffered from @entity1092 -associated acute @entity99 , @entity522 cells were clustered among the @entity39 foci and the foamy cells. In both @entity1 electron microscopy revealed apoptotic nuclei. Normal muscle biopsy specimens were observed in two @entity1 , 2 and 8 years-old respectively; in the 18-year-old @entity1 cytochrome oxidase-negative fibers as well as ultrastructural findings of mitochondrial abnormalities were observed. In no @entity1 was there biochemical evidence of impaired oxidative metabolism. Neuropathological examination of the brains of two @entity1 (13 months and 19 years old, respectively) showed focal distribution of the lesions affecting the @entity4519 cortex and, to a lesser extent, subcortical gray nuclei. Along with the @entity39 lesions, characterized by @entity528 , neuropil microcysts and newly formed vessels, we also observed acutely shrunken neurons and features of apoptotic cell death in the cerebral cortex only. Severe @entity528 without @entity39 features was observed in the cerebellar cortex. The presence of both anoxic and apoptotic nuclei in brain and liver, the target tissues of the disease, is consistent with the hypothesis that abnormal activation of mitochondrion-related cell death pathways might be involved in the pathogenesis of @entity29409 .
