Aicardi-Goutieres Syndrome - The Cause, Disease Progress, Symptoms, Diagnosis, and Treatment Plan

What Is Aicardi-Goutieres Syndrome?

It is an extremely rare genetic disorder that one may be born with. In an Aicardi-Goutieres syndrome-affected individual, the body’s immune system starts to act against oneself to cause destructive reactions. As a result, there may be inflammatory damage inside the brain (encephalopathy). The affected individual suffers problems with their brain, immune system, and skin as well. The child may be born normally without any symptoms, but soon the inflammatory process sets forth and starts damaging the brain. Aicardi-Goutieres syndrome causes high degrees of intellectual disabilities in an individual, along with convulsions, muscle weakness, skin lesions, vision problems, and stiffening of muscles.

What Is the Cause Behind Aicardi-Goutieres Syndrome?

In an Aicardi-Goutieres syndrome-affected individual, a set of genes that control the production of certain enzymes tend to turn defective (mutation). These are the enzymes that help process the waste products from chemical reactions at a cellular level. With a lack of these enzymes, the waste products simply get dumped inside the cells. And the body’s immune mechanism misunderstands them as foreign bodies, just like a virus or bacteria. With the immune system triggered, it sets out high-grade inflammatory reactions. And it tries to destroy the brain cells on the go. Sometimes, the mutation happens to the genes involved in immune system functions as well.

Most individuals get the mutated gene passed on from their parents. If both parents have a copy of the mutated gene, the child has every chance of acquiring Aicardi-Goutieres syndrome. If only one among the parents has the mutated gene in them, the child is not likely to develop it (autosomal recessive). However, there were certain scenarios where an individual suffered spontaneous mutation of the gene without any genetic background of Aicardi-Goutieres syndrome whatsoever. Those with severe neurological dysfunction may not survive beyond childhood. However, those with milder problems may reach adulthood but with intellectual disabilities and brain dysfunction.

What Are the Symptoms of Aicardi-Goutieres Syndrome?

An affected child may not show the symptoms at the time of birth. But in a few weeks to months, they start showing subtle signs of inflammation. Gradually, the symptoms grow severe. Since the condition causes inflammatory damage to the brain, as in an encephalopathy, it may look like the symptoms of this condition mimic that of a viral or bacterial infection affecting the brain. The following are the major symptoms one may show:

• Fever.

• Convulsions and muscle spasms (seizures).

• Uncontrolled twitching of muscles and rigidity of arms and legs, and stiff joints.

• Frequent vomiting.

• Feeding the child becomes difficult.

• Irritability and erratic eye movements.

• Children fail to meet the developmental milestones involving normal muscle movements that aid in walking and performing tasks.

• Problems with speech, learning, and normal social development.

• One may progressively lose the skills they achieved so far (regression).

• Swollen toes and fingers. Sometimes a child may have itchy red skin lesions called chilblains.

• Frequent mouth ulcers.

• The head size of the child may be unusually small as the brain and skull stop growing further.

How Is Aicardi-Goutieres Syndrome Diagnosed?

Since the early signs of Aicardi-Goutieres syndrome resemble that of viral or bacterial encephalopathy, one may find reaching the right diagnosis quite challenging. However, after all the tests to look for the presence of an infectious agent turn negative, one may conclude it is a possible case of Aicardi-Goutieres syndrome. The doctor may conduct the following tests:

1. Clinical and Lab Tests - Look for enlarged liver, spleen, and low platelet (blood cells that help with clotting of blood) levels in the blood.

2. Imaging Studies - Like computed tomography (CT) and magnetic resonance imaging (MRI) scans. This may show typical features of Aicardi-Goutieres syndrome inside the brain. There may be large-scale destruction in the white matter (areas formed by nerve cells covered with a white substance called myelin that helps in signal transfer) in the brain. Also, there will be the presence of calcium deposits inside the brain.

3. Lumbar Puncture (Spinal Tapping) Procedure - It is a test involving the clear fluid known as cerebrospinal fluid (CSF) circulating around the brain and spinal cord. The doctor inserts a needle into one's spinal column in the lower back area and draws a small amount of cerebrospinal fluid. On lab examination of this fluid sample, one may find a marked increase in the number of cells related to the body’s immune system but no traces of bacteria or viruses.

What Is the Treatment for Aicardi-Goutieres Syndrome?

Like any other disease involving death and damage of nerve cells, Aicardi-Goutieres syndrome cannot be cured. One can only control the symptoms with treatment so that the affected child can have an improved living quality. It is mainly a supportive treatment to compensate for the functional deficits caused by neurological damage. The affected child may receive the following:

• Treatment to reduce the impact of inflammatory reactions to ensure the brain damage is as minimal as possible. One may receive Prednisone, Azathioprine, and immunoglobulin G doses for this.

• Treatment and drugs to regulate the occasional seizures.

• Control and regulate other complications from a progressing Aicardi-Goutieres syndrome, such as diabetes, thyroid problems, bone defects, or eyesight issues.

• Assistance with feeding, intubation, and more.

• Assistance with breathing to maintain adequate levels of oxygen in the blood at all times.

• As the child has problems with communication, the family or caregiver of the affected child familiarizes themselves with the facial expressions, certain sounds they make, and the body language of the child to figure out what he or she needs.

• The affected individuals may be given switches to indicate yes or no, or buzz for help. Children are offered picture boards with several drawings and pictures from which they can choose the right picture to communicate their needs.

• At school, the affected children may require specialized classroom equipment and individual instructors.

• Aicardi-Goutieres syndrome is an extremely rare condition; an affected child and their family might feel rather isolated and helpless in their suffering. This is why doctors recommend they reach out to online communities and support groups, including other families with affected children. This way, one can share their concern and explore new ways to improve the quality of the child’s daily living.

Conclusion:

Depending on the severity of the Aicardi-Goutieres syndrome disorder, the complications vary too. Intellectual disability and other neurological problems are lifelong, and one can only provide supportive therapy. Understanding the disease better is one way to realize the challenges faced by an affected child. This way, one can support them better. The doctors advise those with a family history of Aicardi-Goutieres syndrome to undergo genetic counseling before having children. They can explain how the disease gets passed on and what the chances are that one's child may be born with Aicardi-Goutieres syndrome. This may empower the parents to make informed decisions after assessing the risk of passing on gene mutations.