Abstract：
The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to \"TORCH\" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of \"TORCH\" infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi & Goutières, Ann Neurol, 1984;15:49-54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., Ann Neurol, 1998;44:900-907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis.
摘要：
保护性和破坏性免疫反应之间的平衡可能是不稳定的，例如核苷酸代谢中的先天性错误。这类遗传性疾病,模仿感染，可导致全身损伤和严重的神经系统结局。这些疾病中最常见的是AicardiGoutières综合征（AGS）。AGS导致类似于“TORCH”感染的表型(弓形虫，其他[寨卡病毒（ZIKV），人类免疫缺陷病毒（HIV）]，风疹病毒,人巨细胞病毒[HCMV]，和疱疹病毒），但持续的炎症和潜在的并发症。AGS在1980年代初首次被描述为“TORCH”感染的家族性集群，患有严重的神经病,小头畸形,和基底神经节钙化（Aicardi&Goutières，AnnNeurol,1984年；15：49-54），并与慢性脑脊液（CSF）淋巴细胞增多和I型干扰素水平升高有关（Goutières等人。,AnnNeurol,1998；44：900-907）。自从第一次描述以来，AGS的临床范围已从最初的严重损害儿童队列急剧扩展到包括智力一般和轻度痉挛性轻瘫的个体.这种广泛的潜在临床表现可能导致诊断延迟，哪些家庭认为是主要的压力源。此外,针对干扰素信号通路的新兴疗法,及时诊断变得越来越重要.尽管人们对AGS有了很多了解，在我们对病理的细胞型驱动因素以及影响临床结局和实现及时诊断的修饰变量的表征的理解方面仍存在许多差距.
