Biochemical relationships between Reye's and Reye's-like metabolic and toxicological syndromes.
Reye's syndrome is a hepatic encephalopathy with fatty infiltration of the liver and is due to mitochondrial dysfunction. Knowledge of the mechanisms causing Reye's syndrome has been gained from the study of Reye's syndrome-like diseases, including inborn errors of mitochondrial energy production, viral disease and toxicological injury. Entry of fatty acids into mitochondria or beta-oxidation itself may be impaired. Toxins such as hypoglycin, pentanoate, valproate, salicylate, and their metabolites inhibit beta-oxidation pathways and can produce Reye's syndrome-like presentations. Biochemical manifestations of the diverse causes of Reye's syndrome-like disorders are similar and include: hypoglycaemia due to impaired gluconeogenesis, accumulation of fatty acids, fatty acyl CoAs, and acyl carnitines with depletion of free CoA and carnitine. Accumulated products may further injure mitochondria and exacerbate impaired beta-oxidation, uncouple oxidative phosphorylation or increase mitochondrial permeability. Mitochondrial swelling and steatosis of hepatic cells are the histological result. With the advances of biochemical techniques for the study of organic acid excretion patterns, serum fatty acid patterns and identification of enzymatic deficiencies in cells from patients with Reye's syndrome-like presentations, it is clear that Reye's syndrome is, in part, a collection of various inborn errors and toxicological states. Circumstances such as viral disease, prolonged fasting and drugs may precipitate clinical expression of these deficiencies as Reye's syndrome. As work progresses, further causes of Reye's syndrome will be identified.
Osterloh
J
J
Medical Service, San Francisco General Hospital, California.
Cunningham
W
W
Dixon
A
A
Combest
D
D
D000818:Animals; D006801:Humans; D012202:Reye Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology