AGS will arise from a number of genetic mutations expressing key proteins and nucleases. 
- TREX1: 3 repair exonuclease with which acts on single stranded DNA
- RNASEH2A/RNASEH2B/RNASEH2C: endonuclease which acts on oxy ribose nucleotides within RNA: DNA hybrids 
- SAMHD1: Sam and HD domain, containing proteins that act as a deoxynucleoside triphosphate triphosphohydrolase
- ADAR: Enzyme that catalyzes the deamination of adenosine to inosine in dsRNA

Tulane University

AGS is a heritable disease characterized by Mendelian inheritance laws. Clinically, AGS is an inflammatory disorder consisting of microcephaly, spasticity, dystonia psychomotor retardation and childhood death in 35% of cases. Recent evidence links the pathogenesis of AGS, specifically the overproduction of immunostimulatory nucleic acids, to the expression of type I interferon. 

Aicardi Goutieres Syndrome

Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, De Laet C, De Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W Jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013 Dec;12(12):1159-69. doi: 10.1016/S1474-4422(13)70258-8. Epub 2013 Oct 30. PMID: 24183309; PMCID: PMC4349523.

Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study

Underlying Genomic Mutations

Generally, the age of onset of the illness occurs in the first year after birth. However, disease symptoms can be reduced and may stabilize over a period of years. Later onset clinical features-vasculitic lesions (chilblains) and intracranial vasculitis- warrants the immediate development of therapeutics to treat AGS. 

Age of Onset of AGS

A reactive biomarker, specifically the analysis of interferon levels in CSF and serum of patients, may be a potential diagnostic tool to detect the efficacy of therapies. Increased concentrations of interferon alpha present in patient serum with AGS was first published in 1988. This provides the necessary evidence that interferon scores (IS) can be a useful diagnostic technology to measure any improvement of AGS. 

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