What is the pathophysiology of Reye's (Reye) syndrome?

From the Guidelines

Reye's syndrome is a rare but serious condition characterized by acute encephalopathy and fatty liver degeneration, primarily affecting children and teenagers, with a pathophysiology involving mitochondrial dysfunction triggered by viral infections and aspirin use, as described in the study by 1. The condition is characterized by protracted vomiting and encephalopathy in afebrile patients with minimal or absent jaundice, and hepatomegaly in 50% of patients, with key features including:

• Acute non-inflammatory encephalopathy with an altered level of consciousness
• Elevation of ammonia levels 24–48 hours after the onset of mental status changes
• Hepatic dysfunction with a liver biopsy showing fatty metamorphosis or a more than threefold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST) 1. The pathophysiology involves mitochondrial dysfunction triggered by viral infections (particularly influenza or varicella) combined with aspirin use, as noted in the study by 1, which can lead to impaired oxidative phosphorylation, decreased ATP production, and accumulation of ammonia and other toxic metabolites.

Key aspects of the condition

• The resulting cerebral edema causes increased intracranial pressure, leading to neurological symptoms ranging from lethargy to coma
• Hepatocytes develop microvesicular steatosis as fatty acids accumulate, causing liver dysfunction
• Blood ammonia levels rise due to impaired liver function, further contributing to brain toxicity
• The condition can progress rapidly, with mortality rates of 20-40% in severe cases, as reported in the study by 1.

Prevention and management

• Prevention focuses on avoiding aspirin in children with viral illnesses, which has dramatically reduced incidence since the 1980s
• There is no specific treatment for Reye’s syndrome, but key aspects of management include correction of metabolic imbalance and reduction of intracranial pressure, with advice from a specialist in metabolic medicine 1.

From the Research

Pathophysiology of Reye's Syndrome

The pathophysiology of Reye's syndrome is characterized by:

• An acute metabolic encephalopathy, largely affecting children and adolescents 2, 3
• A two-phase illness, almost always associated with a previous viral infection 4
• Insufficient substrate availability, resulting in massive cytotoxic cerebral edema 2
• Mitochondrial disturbance, with the pathophysiologic sequence linking the antecedent viral illness to the mitochondrial injury remaining obscure 2
• Fatty infiltration of the liver and severe edema of the brain 4

Metabolic Disorders

Reye's syndrome has been associated with various metabolic disorders, including:

• Inborn errors of metabolism, such as medium-chain acyl coenzyme A dehydrogenase deficiency 3
• Fatty-acid oxidation defects, which can present as Reye-like syndrome 3
• Organic aciduria, hypoglycemia, and hypoketonemia, often evident in Reye-like syndrome 3

Role of Aspirin

The role of aspirin in Reye's syndrome is controversial, with:

• Some studies suggesting an association between aspirin and Reye's syndrome, but a causal relationship has not been established 2
• Other studies strongly supporting a link between the use of aspirin and Reye's syndrome 4
• Recommendations to avoid the use of aspirin in children exhibiting symptoms suggestive of Reye's syndrome 2, 4