A morphometric study of Reye's syndrome. Correlation of reduced mitochondrial numbers and increased mitochondrial size with clinical manifestations

Abstract

Morphometric analysis of liver ultrastructure in 14 children with Reye's syndrome (RS) of varying morphologic severity was compared with that of 6 children with normal livers. Results showed reduced numbers of enlarged mitochondria in RS. Multivariant analysis identified correlations between increased mitochondrial size, decreased mitochondrial number, and severity of neurologic disease (stage). A disproportionate increase in mitochondrial area and perimeter in the RS cases with the most depressed mitochondrial number distinguished the 4 children with residual neurologic damage or death. Serum salicylate concentrations were negatively correlated with severity of morphologic alteration. Two cases of non-RS salicylate toxicity showed normal or near-normal mitochondrial size and number. In fatty liver from an autopsy specimen from a child, a child with carnitine deficiency, and a child on therapy for dermatomyositis, mitochondrial numbers were also normal. Decreased mitochondrial numbers are characteristic of RS and imply a pathophysiologic mechanism, possibly related to impaired mitochondrial replication. Synergism with other forms of mitochondrial injury, such as salicylates, hypoglycemia, or shock may influence clinical severity, progression, and outcome.