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.