The disorder affects children primarily. Clinical features of RS are relatively stereotyped, at least in children over the age of one year. The cardinal feature is the presence of a biphasic illness. The initial phase consists of a viral infection, usually influenza in epidemic cases and varicella in sporadic cases. These include lethargy, sometimes alternating with hyperactive or combative behavior, followed by obtundation, and in severe cases, stupor or coma.
Seizures are common during the course of the disease, especially in young children.
There is laboratory evidence of hepatic dysfunction in virtually all cases, with elevated serum transaminases, prolonged prothrombin time, and hyperammonemia. However, bilirubin concentrations are normal. Hypoglycemia may be present early in the course of the encephalopathy, particularly in children under the age of 4 years. Infants under one year of age may have a different clinical presentation, with little or no vomiting, but with sudden onset of encephalopathy following a viral infection. Respiratory difficulties, including hyperventilation and sudden apnea, are prominent.