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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Neurology

Understanding Your Tests and Diagnosis

At a Glance

Aicardi-Goutières syndrome (AGS) is diagnosed using a combination of brain imaging, specialized blood tests, and genetic sequencing. Doctors look for brain calcifications and a high 'interferon signature' in the blood, but a genetic test is required to officially confirm the exact mutation.

Diagnosing Aicardi-Goutières syndrome (AGS) is a process of putting together pieces of a puzzle. Because it is so rare and often looks like other conditions, doctors use a combination of brain imaging, specialized blood tests, and genetic confirmation to be certain [1][2].

The Clinical Diagnosis: Brain and Body

A clinical diagnosis is based on what the doctor can see through exams and scans.

  • Brain Imaging (MRI or CT): Doctors look for three hallmark signs:
    • Calcifications: Small “calcium spots” that usually appear in the basal ganglia (a part of the brain that helps with movement) [2][3].
    • Leukoencephalopathy: This is a broad term for abnormalities in the “white matter,” the parts of the brain that send messages from one area to another [4][5].
    • Cerebral Atrophy: This means some parts of the brain are smaller than expected for the child’s age [4][6].
  • Cerebrospinal Fluid (CSF) Testing: A spinal tap allows doctors to test the CSF, the fluid that cushions the brain. In children with active AGS, this fluid often shows:
    • Lymphocytosis: An unusually high number of white blood cells (lymphocytes), which is a sign of inflammation [7][1].
    • Elevated IFN-alpha: High levels of interferon-alpha, the “viral alarm” protein [4][8].

The Laboratory Key: The Interferon Signature

One of the most important tools for diagnosing AGS is the interferon signature blood test [9]. This test doesn’t look for a virus; instead, it measures how many “interferon-stimulated genes” (ISGs) are turned on in the blood [10][11]. A high “interferon score” tells doctors that the body’s immune system is stuck in an overactive, “alarm” state [12][13].

The Molecular Diagnosis: Genetics

While scans and blood tests suggest AGS, a molecular diagnosis (genetic testing) is the only way to confirm it definitively [14][4].

  • Whole Exome Sequencing (WES): This is a powerful test that looks at all the genes in the body to find the specific mutation causing the problem [15][16].
  • Targeted Panels: Sometimes doctors use a “leukodystrophy panel” or an “AGS panel” that focuses only on the nine known genes linked to the condition [4][17].

Newly Diagnosed Completeness Checklist

If your child has just been diagnosed, ensure the following have been completed or scheduled:

  1. [ ] Genetic Confirmation: Identification of the specific gene (e.g., TREX1, RNASEH2B, etc.) [4].
  2. [ ] Baseline Brain Imaging: An MRI or CT scan to document any current calcifications or white matter changes [9].
  3. [ ] Interferon Signature Test: A blood test to establish your child’s “baseline” inflammation level [10].
  4. [ ] Organ Screenings:
    • Liver: Blood test for liver enzymes [18].
    • Thyroid: Screening for hypothyroidism [19].
    • Kidneys: Monitoring for signs of kidney involvement (especially for RNASEH2B or RNU7-1 types) [20][8].
  5. [ ] Vascular Imaging: If your child has the SAMHD1 mutation, specialized imaging (MRA) to check the health of their brain’s blood vessels [21][22].
  6. [ ] Genetic Counseling: A meeting to understand how the gene was inherited and what it means for siblings or future children [16].

Common questions in this guide

What is the interferon signature test for AGS?
The interferon signature is a specialized blood test that measures how many interferon-stimulated genes are active. A high score shows the immune system is stuck in an overactive alarm state, which is a key indicator of Aicardi-Goutières syndrome.
What will a brain MRI show if my child has AGS?
An MRI may show three hallmark signs of AGS: calcium spots in the basal ganglia, abnormalities in the brain's white matter (leukoencephalopathy), and areas of the brain that are smaller than expected for the child's age (cerebral atrophy).
Why is genetic testing necessary for an AGS diagnosis?
While scans and blood tests can strongly suggest Aicardi-Goutières syndrome, genetic testing is the only way to definitively confirm the diagnosis. It identifies the exact gene mutation causing the condition, which is essential for guiding treatment and monitoring.
What organ screenings are needed after an AGS diagnosis?
Newly diagnosed patients should undergo baseline blood tests to screen liver enzymes and thyroid function, as well as monitoring for kidney involvement. Depending on the specific gene mutation, specialized vascular imaging may also be needed to check the brain's blood vessels.

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What Is the Interferon Signature Test for AGS?

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific AGS gene was identified, and does it mean we need to check other organs like the heart or kidneys?
  2. 2.Is the 'interferon signature' test being used to monitor how well the current treatment is working?
  3. 3.Can you explain the specific findings on our child's MRI, and how they relate to the symptoms we are seeing?
  4. 4.Are we past the point where a CSF (spinal tap) is necessary for diagnosis?

References

References (22)
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    Clinical and neuroradiologic variability of Aicardi-Goutiéres syndrome: Two siblings with RNASEH2C mutation and a boy with TREX1 mutation.

    Uyur Yalçın E, Maraş Genç H, Kara B

    The Turkish journal of pediatrics 2015; (57(5)):504-8.

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    TREX-1 related Aicardi-Goutières syndrome improved by Janus kinase inhibitor.

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    American journal of medical genetics. Part A 2024; (194(5)):e63510 doi:10.1002/ajmg.a.63510.

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    Aicardi-Goutières syndrome: A monogenic type I interferonopathy.

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    Scandinavian journal of immunology 2023; (98(4)):e13314 doi:10.1111/sji.13314.

    PMID: 37515439
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    Generation of three induced pluripotent cell lines (iPSCs) from an Aicardi-Goutières syndrome (AGS) patient harboring a deletion in the genomic locus of the sterile alpha motif and HD domain containing protein 1 (SAMHD1).

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    Stem cell research 2020; (43()):101697 doi:10.1016/j.scr.2019.101697.

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    Short-term efficacy of tofacitinib, a JAK inhibitor, in IFIH1-related Aicardi-Goutières syndrome.

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    [Aicardi-Goutieres syndrome due to mutation of the IFIH1 gene with pontine involvement. A case report].

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    Mutations in RNU7-1 Weaken Secondary RNA Structure, Induce MCP-1 and CXCL10 in CSF, and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement.

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    PNPT1 mutations may cause Aicardi-Goutières-Syndrome.

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    Sine causa tetraparesis: A pilot study on its possible relationship with interferon signature analysis and Aicardi Goutières syndrome related genes analysis.

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    Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.

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    Phenotypic and Molecular Spectrum of Aicardi-Goutières Syndrome: A Study of 24 Patients.

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    An overview of genetic mutations in Aicardi-Goutières syndrome in Iranian population.

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    The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.

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    Collapsing Glomerulopathy as a Complication of Type I Interferon-Mediated Glomerulopathy in a Patient With RNASEH2B-Related Aicardi-Goutières Syndrome.

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This page provides educational information about Aicardi-Goutières syndrome testing and diagnosis. Always consult your pediatric neurologist or medical geneticist to interpret your child's specific diagnostic results.