Reye's Syndrome

What Causes Reye’s Syndrome?

Scientists don’t know precisely what causes RS. The condition usually occurs when several different factors intersect. It most often occurs when aspirin is used to treat symptoms after a child has experienced a viral infection such as influenza or chickenpox. It also often occurs in children who have an inherited disorder that limits their body’s ability to break down certain fatty acids; these disorders are called fatty acid oxidation disorders. However, the precise way that these factors come together to cause RS is not clear.

Is Reye’s Syndrome Hereditary?

Reye’s Syndrome itself may not be inherited, but the metabolic disorders that appear to play a part in triggering the syndrome can be. These disorders, the most common of which is medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, can also cause symptoms similar to those of RS. MCAD is passed on from parent to child when each parent carries one copy of the gene that causes the disorder. In this case, the parents themselves usually don’t show symptoms of the condition.

How Is Reye’s Syndrome Detected?

Early diagnosis and treatment of RS are vital. If left untreated, RS can be fatal within days. Parents should consult a doctor if their child shows symptoms after a viral infection like the flu or chickenpox. Signs to watch for include:

• Vomiting
• Sleepiness or lethargy
• Changes in behavior

Children who exhibit more severe symptoms after a viral infection should receive immediate emergency medical attention. Symptoms requiring emergency care include:

• Seizures
• Loss of consciousness

How Is Reye’s Syndrome Diagnosed?

No test or exam directly detects RS. The diagnostic process typically includes a series of tests and exams to look for the underlying metabolic factors characteristic of the disorder and tests to look for symptoms caused by RS. Common diagnostic steps include:

Blood, urine, and stool tests. These tests look for signs of abnormal liver function.

Liver biopsy. This test involves removing a small sample of liver tissue and examining it for changes that sometimes occur in conjunction with RS.

Electroencephalogram (EEG). This test measures the brain’s electrical activity.

Lumbar puncture (spinal tap) and/or intracranial pressure monitoring (ICP). These procedures measure the pressure of fluid in the brain, which is elevated in RS cases.

Imaging exams such as magnetic resonance imaging (MRI) or computerized tomography (CT). These exams may be able to detect swelling of the brain and liver.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Reye’s Syndrome Treated?

There is no cure for RS. Treatment of the disorder focuses on alleviating symptoms and controlling brain swelling to prevent complications or death. Common treatment options include:

• Hospitalization (often in an intensive care unit) for close monitoring of symptoms
• Administration of intravenous glucose
• Diuretic medications to lessen the accumulation of fluid in the brain
• Anti-seizure medications
• Medications to treat problems with liver function
• Mechanical breathing assistance

How Does Reye’s Syndrome Progress?

When RS is treated early, recovery is common. However, if symptoms are not treated quickly, brain swelling can progress rapidly and is often fatal within days. When RS is not treated promptly or when symptoms progress to the point the child lapses into a coma, the chance of recovery is significantly reduced.

Many people recover fully from RS without any long-term complications. If brain swelling is severe and/or prolonged, permanent brain damage may result. Permanent liver damage is also possible.

How Is Reye’s Syndrome Prevented?

Aspirin appears to be a key factor in the development of RS. Parents should avoid giving aspirin to children, and aspirin should never be used to treat the symptoms of flu or chickenpox even after a child seems to have recovered from the illness.

All forms of aspirin should be avoided, including those labeled as acetylsalicylic acid, acetylsalicylate, salicylic acid, and salicylate. Many over-the-counter medications contain aspirin, even though their packaging may not make it clear.

Alternative over-the-counter medications for pain and fever include acetaminophen and ibuprofen.

Children with conditions that require aspirin for treatment should be vaccinated to prevent the infections commonly associated with RS.

Screening for fatty acid oxidation disorders can identify children who are at increased risk of RS.

Reye’s Syndrome Caregiver Tips

Parents can take steps to decrease the risk of their child developing Reye’s Syndrome.

• Be aware of the disorder, its symptoms, its risk factors, and its potential complications. The National Reye’s Syndrome Foundation maintains an informational website to guide parents in learning about the condition.
• Be alert for signs of the disorder in your child and act quickly if you see them.
• Avoid giving your child aspirin, especially during or following an illness. Be aware of the different names for aspirin, and make sure to avoid medications that contain it.
• Ensure your child is vaccinated against influenza, chickenpox, and other viral diseases.

Some people with Reye’s syndrome also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with RS:

• Children who have had Reye’s syndrome are at increased risk of anxiety and depression.
• Parents of children who survive RS are more likely than their children to experience anxiety and depression later.

Reye’s Syndrome Brain Science

The effects of RS on the brain are probably the result of a chain of events in the body after a viral infection. Scientists think that the chain of events begins when there is damage to mitochondria, the structures in the body’s cells responsible for converting certain compounds to energy. The mitochondrial damage inhibits the cells’ ability to break down fatty acids properly. The damage is already present in people with fatty acid oxidation disorders. Viral infections and aspirin may make the damage worse.

When cells are unable to break down fatty acids, several chemical changes occur in the bloodstream. Researchers believe that a key factor is an elevated level of ammonia in the blood. High ammonia levels cause swelling in cells (astrocytes) responsible for removing ammonia from the blood. Astrocyte swelling, in turn, causes cerebral edema, the potentially fatal accumulation of fluid in the brain.

Reye’s Syndrome Research

Title: Longitudinal Study of Mitochondrial Hepatopathies (MITOHEP)

Stage: Recruiting

Principal investigator: Kasper Wang, MD 

Children’s Hospital Los Angeles

Los Angeles, CA

The specific aims of this study are (1) to determine the clinical phenotypes and natural history of hepatic RC and FAO disorders, (2) to determine the correlation between genotype and phenotype, (3) to determine if circulating biomarkers reflect diagnosis and predict liver disease progression and survival with the native liver, (4) to determine the clinical outcome of these disorders following liver transplantation, and (5) to develop a repository of serum, plasma, urine, tissue, and DNA specimens that will be used in ancillary studies. To accomplish these aims, the ChiLDREN investigators at clinical sites (currently 15 sites) will prospectively collect defined data and specimens in a uniform fashion at fixed intervals in a relatively large number of subjects. Clinical information and DNA samples to be collected from subjects and their parents will enhance the potential for meaningful research in these disorders. A biobank of subject specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study.

Title: Brain Biomarkers Study

Stage: Recruiting

Principal Investigator: Nicholas Ah Mew, MD 

Children’s National Research Institute

Washington, DC

Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. The following aims are proposed:

Aim 1 of this study will determine the chronology of biomarkers of brain injury in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder.

Aim 2 will determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).

Title: A Study of the Safety of REN001 in Patients With Fatty Acid Oxidation Disorders

Stage: Recruiting

Principal Investigator:  Aaina Kochar, MD

Children’s Hospital Colorado

Aurora, CO

This is a Phase 1, open-label, multiple-dose study of the safety and tolerability of 2 dose levels of REN001 in subjects with fatty acid oxidation disorders (FAODs) with confirmed mutations in the Carnitine palmitoyltransferase II deficiency (CPT2), Very long-chain Acyl-CoA dehydrogenase deficiency (VLCAD), Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) or Trifunctional Protein Deficiency (TFP). All subjects will provide written consent before commencing any study-related activities or assessments. Potential subjects will be screened for study participation up to 8 weeks before the start of dosing. The study is divided into two parts, Part A and Part B. Part A has finished enrollment and further eligible patients will participate in Part B only.