Encephalopathy of Reye's syndrome: a review of pathogenetic hypotheses.
The pathogenesis of Reye's syndrome encephalopathy was analyzed in terms of uniform criteria designed to clarify and assist evaluation of the leading hypotheses. Three of these hypotheses derive from known metabolic sequelae of hepatic mitochondrial dysfunction and the severe systemic catabolism of protein, fats, and carbohydrates that characterize the syndrome biochemically: hyperammonemia, hyperfattyacidemia, and hyperlactatemia. In addition, there is a fourth hypothesis of generalized mitochondrial insult affecting brain, muscle, and other organs as well as liver. The weight of evidence favors hyperammononemia as a sufficient factor while recognizing important interrelationships with the other observed biochemical derangements. How the catabolism and hepatic mitochondrial dysfunction are produced by the triggering viral infection remains unknown. Therapeutic efforts have thus far not succeeded in definitive metabolic intervention. Such reversal of the clinical syndrome would lead to confirmation of the necessary pathogenetic factors; this type of intervention remains the chief goal of metabolic research in Reye's syndrome.
D000138:Acidosis / Q000150:complications; D000641:Ammonia / Q000009:adverse effects / Q000097:blood*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002956:Citrulline / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007427:Intracranial Pressure; D007773:Lactates / Q000097:blood; D008928:Mitochondria / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000201:enzymology; D009584:Nitrogen / Q000378:metabolism; D009952:Ornithine / Q000378:metabolism; D011817:Rabbits; D012202:Reye Syndrome / Q000097:blood / Q000188:drug therapy / Q000209:etiology*
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D002956:Citrulline; D000641:Ammonia; D009952:Ornithine; D005947:Glucose; D009584:Nitrogen