Reye’s syndrome is characterized by acute encephalopathy and fatty degeneration of the liver. The CDC now define Reye syndrome as an acute non-inflammatory encephalopathy (alteration in level of consciousness, no CSF pleocytosis and, if biologic examination is possible. cerebral edema without meningeal or perivascular inflammation) associated with “microvesicular fatty metamorphosis of the liver” (confirmed by biopsy or autopsy) or a significant rise (threefold or greater) of serum transaminases or blood ammonia, and having “no more reasonable explanation” for the cerebral and hepatic abnormalities. The disorder is associated with salicylate ingestion and influenza B virus. An increasing number of inherited mitochondrial metabolic diseases have been described that produce episodes like Reye’s syndrome of which the main disorders are disorders of fatty acid oxidation, disorders of oxidative phosphorylation, urea cycle defects, organic acidurias and general mitochondrial dysfunction. The pathophysiology involves generalized loss of mitochondrial function leading to disturbances in fatty acid and carnitine metabolism.

“Classic” Reye’s syndrome was seen with influenza B and varicella infection in children between 4-12 years of age. It has a stereotypic biphasic course. When the child is seemingly recovering from a prodromal febrile illness, abrupt onset of protracted vomiting occurs. Delirium, combative behavior and stupor may occur simultaneously or within few hours after onset of vomiting. Neurologic symptoms may rapidly progress to seizures, coma and death (focal neurologic signs are absent). There is a mild hepatomegaly and patients remain anicteric. There is increase in serum aminotransferases, creatine kinase and lactic dehydrogenase with hyperammonia. Younger patients have hypoglycemia (they should be screened for metabolic disease). Biopsy may be required to rule out metabolic or toxic liver disease especially in patients younger than 1-2 years. The major site of injury is the mitochondria. The hepatic intramitochondrial enzymes including ornithine transcarbamylase (OTC), carbamoylphosphate synthetase (CPS) and pyruvate dehydrogenase are reduced leading to hyperammonemia. Aspirin has been found to be associated with this mitochondrial dysfunction and it is prudent to avoid aspirin in patients with varicella or influenza. A child with Reye’s syndrome should be screened for metabolic disorder and baseline urinary organic acid, serum and urine carnitine, urinary ketones, serum free fatty acids, serum amino acids and serum lactate and pyruvate are necessary. Specialized tests such as Long chain fatty acid loading test, protein load test, urinary orotic acid and enzymatic analysis may be required as necessary. Treatment consists of control of increased intracranial pressure, glucose administration and management of coagulopathy. Pentobarbital may have a protective effect on the CNS by decreasing cerebral metabolic demands, decreasing cerebral blood flow and causing cerebral vasoconstriction.