Aicardi-Goutieres syndrome

An inherited encephalopathy, the most severe form of which is characterized by cerebral atrophy, leukodystrophy, intracranial calcifications, and chronic cerebrospinal fluid LYMPHOCYTOSIS. Although AGS presents similarly to in utero viral infection, patients are negative for prenatal infections . MICROCEPHALY and neurologic dysfunction occurs later in infancy. Other abnormalities include THROMBOCYTOPENIA, hepatosplenomegaly, elevated hepatic transaminases, and intermittent fever. Mutations in the TREX1, RNASEH2A, RNASEH2B, and RNASEH2C genes have been identified. OMIM: 225750

Also Known As:

Networked: 38 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Systemic Lupus Erythematosus (Libman-Sacks Disease)
2.	Brain Diseases (Brain Disorder)
3.	Chilblain lupus 1
4.	Microcephaly
5.	Bites and Stings (Sting)

Experts

1.	Hollis, Thomas: 3 articles (12/2011 - 05/2011)
2.	Perrino, Fred W: 3 articles (12/2011 - 05/2011)
3.	Lebon, P: 3 articles (08/2008 - 03/2003)
4.	Fazzi, Elisa: 2 articles (01/2021 - 01/2012)
5.	Orcesi, Simona: 2 articles (01/2021 - 01/2012)
6.	Balci, Sibel: 2 articles (09/2020 - 12/2017)
7.	Bisgin, Atil: 2 articles (09/2020 - 12/2017)
8.	Kisla Ekinci, Rabia Miray: 2 articles (09/2020 - 12/2017)
9.	Yilmaz, Mustafa: 2 articles (09/2020 - 12/2017)
10.	Chen, Qi: 2 articles (01/2020 - 01/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Aicardi-Goutieres syndrome:

1.	Ubiquitin-Specific ProteasesIBA 04/01/2022 - "In this study, a familial case of pseudo-TORCH syndrome 2 with novel non-sense mutation in the ubiquitin-specific peptidase 18 (USP 18) gene in the parents was reported, who are heterozygous asymptomatic carriers; however, all children have inherited a homozygous pathogenic form of USP18, which is an important negative regulator of type I interferon (IFN) signal transduction. " 01/01/2017 - "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed "interferonopathies" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency. "
2.	Interferon Type IIBA 04/01/2022 - "In this study, a familial case of pseudo-TORCH syndrome 2 with novel non-sense mutation in the ubiquitin-specific peptidase 18 (USP 18) gene in the parents was reported, who are heterozygous asymptomatic carriers; however, all children have inherited a homozygous pathogenic form of USP18, which is an important negative regulator of type I interferon (IFN) signal transduction. " 01/01/2022 - "This review provides insights into the pathogenesis and genetic causes of these "prototypic" diseases caused by gain-of function mutations in IL-1-activating inflammasomes (inflammasomopathies) and in interferon-activating pathways (interferonopathies) including STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and proteasome-associated autoinflammatory syndromes that link activation of the viral sensors STING, "self" nucleic acid metabolism, and the ubiquitin-proteasome system to "type I interferon production" and human diseases. "
3.	Interferon-alpha (Interferon Alfa)IBA 03/01/2003 - "We report that levels of interferon alpha (IFN-alpha), a marker of AGS, are raised in Cree encephalitis. " 03/01/2003 - "Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism." 02/01/2005 - "These findings add support to the suggestion that Aicardi-Goutieres syndrome and systemic lupus erythematosus are closely related disorders in which dysregulated production of interferon-alpha might play a crucial role." 04/01/2005 - "Aicardi-Goutieres syndrome is a familial progressive early onset encephalopathy with basal ganglia calcifications, chronic CSF lymphocytosis and high level of interferon-alpha in CSF. " 10/01/2016 - "Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. "
4.	Proteins (Proteins, Gene)FDA Link 01/01/2021 - "Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KI20A and UBP18), and ZIKV induces potential entry factor PLVAP. " 06/06/2023 - "The results showed that the induced pluripotent stem cell line of Aicardi-Goutieres syndrome was successfully constructed and showed typical embryonic stem-like morphology after stable passage, RT-PCR showed mRNA expression of stem cell markers, AP staining was positive, OCT4, SOX2, NANOG, SSEA4, TRA-1-81 and TRA-1-60 pluripotency marker proteins were strongly expressed. " 02/28/2018 - "While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. " 02/16/2016 - "Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. "
5.	InterferonsIBA 01/01/2013 - "Chronic exposure of astrocytes to interferon-α reveals molecular changes related to Aicardi-Goutieres syndrome." 01/01/2017 - "Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed "interferonopathies" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency. " 12/01/2014 - "One such sensor referred to as STING (for stimulator of interferon genes) has been found to be seminal for controlling cytosolic-DNA induced cytokine production, and may be responsible for a wide variety of inflammatory diseases including systemic lupus erythematosus (SLE), Aicardi-Goutieres syndrome (AGS) and STING-associated vasculopathy with onset of infancy (SAVI). " 01/01/2022 - "This review provides insights into the pathogenesis and genetic causes of these "prototypic" diseases caused by gain-of function mutations in IL-1-activating inflammasomes (inflammasomopathies) and in interferon-activating pathways (interferonopathies) including STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and proteasome-associated autoinflammatory syndromes that link activation of the viral sensors STING, "self" nucleic acid metabolism, and the ubiquitin-proteasome system to "type I interferon production" and human diseases. "
6.	DNA (Deoxyribonucleic Acid)IBA 10/01/2014 - "Exome sequencing of the proband's blood DNA showed a homozygous c.626-1G > C mutation in intron 5 of the SAMHD1 gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi-Goutieres syndrome. " 01/01/2019 - "Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). " 12/01/2014 - "One such sensor referred to as STING (for stimulator of interferon genes) has been found to be seminal for controlling cytosolic-DNA induced cytokine production, and may be responsible for a wide variety of inflammatory diseases including systemic lupus erythematosus (SLE), Aicardi-Goutieres syndrome (AGS) and STING-associated vasculopathy with onset of infancy (SAVI). " 01/01/2020 - ": 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive."
7.	Ribonucleases (Ribonuclease)IBA 05/13/2011 - "Functional consequences of the RNase H2A subunit mutations that cause Aicardi-Goutieres syndrome." 01/01/2012 - "Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in Aicardi-Goutieres syndrome." 02/16/2016 - "Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. "
8.	Nucleic AcidsIBA 10/15/2009 - "Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity." 02/16/2016 - "Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. " 01/01/2022 - "This review provides insights into the pathogenesis and genetic causes of these "prototypic" diseases caused by gain-of function mutations in IL-1-activating inflammasomes (inflammasomopathies) and in interferon-activating pathways (interferonopathies) including STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and proteasome-associated autoinflammatory syndromes that link activation of the viral sensors STING, "self" nucleic acid metabolism, and the ubiquitin-proteasome system to "type I interferon production" and human diseases. "
9.	three prime repair exonuclease 1IBA 09/16/2011 - "Dominant mutation of the TREX1 exonuclease gene in lupus and Aicardi-Goutieres syndrome." 01/01/2012 - "Different mutations in three prime repair exonuclease 1 and ribonuclease H2 genes affect clinical features in Aicardi-Goutieres syndrome." 01/01/2020 - "Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. "
10.	OccludinIBA 12/10/2010 - "Their clinical presentation overlaps with some reported cases of pseudo-TORCH syndrome as well as with cases involving mutations in occludin, another component of the tight-junction complex. " 01/01/2016 - "Band like calcification with simplified gyration and polymicrogyria (BLC-PMG) is a distinct neuroradiological phenotype initially reported as a pseudo-TORCH syndrome and known to result from biallelic mutations in the Occludin(OCLN) gene. "

Therapies and Procedures

1.

Therapeutics 01/01/2020 - ": 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive."