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Case Reports
. 2022 Jul;18(7):490-497.
doi: 10.1007/s12519-022-00545-1. Epub 2022 May 12.

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China

Wei Wang  1   2 , Wei Wang  1   2 , Ting-Yan He  1   2 , Li-Ping Zou  3 , Wen-Dao Li  1   2 , Zhong-Xun Yu  1   2 , Ming-Sheng Ma  1   2 , Jun Yang  4 , Hong-Mei Song  5
Affiliations
Case Reports

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China

Wei Wang et al. World J Pediatr. 2022 Jul.

Abstract

Background: Aicardi-Goutieres syndrome (AGS) is an inflammatory disorder belonging to the type I interferonopathy group. The clinical diagnosis of AGS is difficult, which can lead to a high mortality rate. Overall, there is a lack of large-sample research data on AGS in China. We aim to summarize the clinical characteristics of Chinese patients with AGS and provide clues for clinical diagnostic.

Methods: The genetic and clinical features of Chinese patients with AGS were collected. Real-time polymerase chain reaction was used to detect expression of interferon-stimulated genes (ISGs).

Results: A total of 23 cases were included, consisting of 7 cases of AGS1 with three prime repair exonuclease 1 mutations, 3 of AGS2 with ribonuclease H2 subunit B (RNASEH2B) mutations, 3 of ASG3 with RNASEH2C, 1 of AGS4 with RNASEH2A mutations, 2 of AGS6 with adenosine deaminase acting on RNA 1 mutations, and 7 of AGS7 with interferon induced with helicase C domain 1 mutations. Onset before the age of 3 years occurred in 82.6%. Neurologic involvement was most common (100%), including signs of intracranial calcification which mainly distributed in the bilateral basal ganglia, leukodystrophy, dystonia, epilepsy, brain atrophy and dysphagia. Intellectual disability, language disability and motor skill impairment were also observed. Skin manifestations (60.87%) were dominated by a chilblain-like rash. Features such as microcephaly (47.62%), short stature (52.38%), liver dysfunction (42.11%), thyroid dysfunction (46.15%), positive autoimmune antibodies (66.67%), and elevated erythrocyte sedimentation rate (53.85%) were also found. The phenotypes of 2 cases fulfilled the diagnostic criteria for systemic lupus erythaematosus (SLE). One death was recorded. ISGs expression were elevated.

Conclusions: AGS is a systemic disease that causes sequelae and mortality. A diagnosis of AGS should be considered for patients who have an early onset of chilblain-like rash, intracranial calcification, leukodystrophy, dystonia, developmental delay, positive autoimmune antibodies, and elevated ISGs, and for those diagnosed with SLE with atypical presentation who are nonresponsive to conventional treatments. Comprehensive assessment of vital organ function and symptomatic treatment are important.

Keywords: Aicardi-Goutieres syndrome; Chinese; Diagnosis; Manifestations.

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Conflict of interest statement

Author SHM is a member of the Editorial Board for World Journal of Pediatrics. The paper was handled by the other Editor and has undergone rigorous peer review process. Author SHM was not involved in the journal's review of, or decisions related to, this manuscript. No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Real-time polymerase chain reaction detection of relative expression of ISGs in six patients, including two with AGS1 (P1 and P3) and four with AGS7 (P17, P21, P22 and P23). a IFIT1; b IFI27; c IFI44L; d ISG15; e RSAD2. IFI interferon alpha-inducible protein encoding gene, ISGs interferon-stimulated genes, RSAD2 radical S-adenosyl methionine domain containing 2 encoding gene
See this image and copyright information in PMC

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References

    1. Aicardi J, Goutières F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol. 1984;15:49–54. doi: 10.1002/ana.410150109. - DOI - PubMed
    1. Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015;167A:296–312. doi: 10.1002/ajmg.a.36887. - DOI - PMC - PubMed
    1. Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, et al. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet. 2007;81:713–725. doi: 10.1086/521373. - DOI - PMC - PubMed
    1. Rice GI, Kasher PR, Forte GM, Mannion NM, Greenwood SM, Szynkiewicz M, et al. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nat Genet. 2012;44:1243–1248. doi: 10.1038/ng.2414. - DOI - PMC - PubMed
    1. Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, et al. Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet. 2009;41:829–832. doi: 10.1038/ng.373. - DOI - PMC - PubMed

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