What Is Aicardi-Goutières Syndrome (AGS)?

What Is Aicardi-Goutières Syndrome (AGS)?
What Is Aicardi-Goutières Syndrome (AGS)?

An uncommon neurological disorder called Aicardi-Goutières syndrome results in both physical and intellectual incapacity. Although there isn't a cure, managing symptoms can enhance life expectancy.

Gene mutations that are passed down through families produce the progressive genetic brain disease known as Aicardi-Goutières syndrome (AGS). There are various additional names for it, including:
  • Cree encephalitis
  • pseudotoxoplasmosis syndrome
  • basal ganglia calcification encephalopathy
Interferons are molecules that are produced in excess in children with AGS. Normally, a virus infection of a healthy cell results in the production of interferons. By "interfering," these interferons prevent a virus from proliferating. Excessive interferon production, however, can induce brain damage that frequently results in significant intellectual and physical impairment.

AGS is an extremely uncommon illness. Although exact incidence rates in the US and around the world are unknown, researchers predicted in a 2022 study that it affects less than 1 in 100,000 infants in Denmark.

Types of AGS

Mutations in any one of multiple genes cause AGS. The accumulation of calcium in the brain is caused by these genetic abnormalities. It is believed that this accumulation sets off an autoimmune reaction brought on by an increase in alpha-interferon production.

Normally, these interferon molecules alert your immune system to the presence of viruses that require elimination. When a person has AGS, their immune system goes into overdrive, attacking a fictitious virus that causes harm to healthy brain tissue.

AGS belongs to a class of diseases known as interferonopathies, which are all defined by dysregulation of interferon.

There are two types of AGS: early-onset and later-onset.
  • Early-onset: The early-onset kind usually manifests with more severe symptoms from birth. It frequently results in serious physical and mental impairment. About 20% of cases involve it.
  • Later-onset: Within weeks to months after birth, the later-onset variant manifests. Even though the symptoms are usually less severe, it can yet result in crippling neurological issues.

What are the symptoms of AGS?

Those with early-onset AGS typically have more severe symptoms. Severe physical and intellectual disabilities may result from it.

Early-onset AGS may manifest with symptoms and indicators like:
  • rashes
  • seizures
  • jittery behaviour
  • liver inflammation
  • infants' inadequate feeding abilities
  • a head that is smaller than usual (microcephaly)
  • anomalies of the liver and nervous system from birth
The following are some indications and symptoms of later-onset AGS:
  • delayed head growth
  • seizures
  • strained and feeble muscles (spasticity)
  • Anger and sobbing uncontrollably
  • intermittent fever without apparent cause
  • rashes, chilblains, or cold-related edoema in the fingers, toes, or ears
AGS may result in further issues including:
  • diabetes
  • scoliosis
  • glaucoma
  • platelet problems
  • underactive thyroid
  • Heart, lung, or vascular issues

What causes AGS?

One or more gene mutations are the cause of AGS. At least nine genes have been linked by researchers to AGS, and they are as follows:
  • TREX1
  • SAMHD1
  • ADAR
  • IFIH
  • LSM11
  • RNU7-1
Gene mutations linked to AGS typically exhibit a recessive inheritance pattern that is passed down through families. To develop AGS, you need one linked gene from each parent.

Less frequently, AGS might arise from random mutations that don't have a familial history. Certain gene mutations are dominant, which means that all it takes to develop AGS is inheriting them from one parent. Among these are mutations in the genes listed below:
  • ADAR
  • TREX1
  • IFIH
A family history is the only known risk factor for AGS, and the condition appears to affect men and women about equally.

How is it diagnosed?

AGS may be suspected by a physician based on your child's symptoms and indicators. Laboratory tests and imaging can bolster their diagnosis.

The two most popular imaging techniques are computed tomography (CT) and magnetic resonance imaging (MRI). They can disclose common characteristics like:
  • calcification of the brain's spinal nerves
  • alterations to your brain's white matter throughout
  • loss of cerebral mass
The following laboratory results can help confirm an AGS diagnosis:
  • blood cell abnormalities
  • elevated liver enzymes
  • increased number of white blood cells in the cerebral spinal fluid
  • elevated neopterin and interferon-alpha levels
Genetic tests to search for gene mutations known to cause AGS help confirm the diagnosis.

It is uncommon for AGS to be identified before childbirth. In a 2023 case study, researchers used the findings of a genetic test in conjunction with an ultrasound to diagnose AGS in utero in a child.

Can it be treated?

The main goals of AGS treatment are to manage symptoms and enhance overall quality of life. Options include:
  • antiseizure medications
  • physiotherapy to improve movement
  • respiratory physical therapy to enhance respiration
  • keeping an eye on nutritional condition and providing nutritional assistance
  • Myorelaxants and botulinum toxin for the treatment of muscular spasticity
It appears that AGS does not react well to conventional immunosuppressive drugs. According to some recent data, Janus kinase inhibitors might aid in the suppression of interferon activity. Baricitinib, a particular type of Janus kinase inhibitor, may aid in the development of new motor abilities in AGS patients.

Researchers discovered encouraging outcomes with tocilizumab, a kind of monoclonal antibody, in a 2023 study.

Enrolling your child in a clinical study may provide your child with access to novel treatments as well as aid researchers in their understanding of AGS.

You can check the National Institutes of Health website for a list of ongoing clinical studies, or you can ask your doctor about clinical trials for which your kid could qualify.

What is the outlook for someone with AGS syndrome?

AGS children frequently suffer from serious physical and intellectual disabilities. The majority of kids don't make it past childhood. Milder types of the condition can cause a person to live into maturity, and there have even been a few documented cases of AGS patients with normal IQ.

It is very unlikely for children with early-onset AGS to live to adulthood. Frequently, they die in the first year of life.


An autoimmune anomaly is the root cause of AGS, an uncommon neurological disorder. There is presently no known treatment for it, and many children suffer from serious mental and physical disabilities.

Enrolling your child in a clinical study may provide your child with access to novel medicines as well as aid researchers in better understanding the illness. Your child's eligibility for clinical trials can be discussed with your physician.

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