Aicardi-Goutieres syndrome
Aicardi-Goutieres syndrome
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DOI：
10.1093/bmb/ldn049
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发表时间：
2009-03-01
影响因子：
6.7
通讯作者：
Fazzi, E.
中科院分区：
文献类型：
--
作者：
Orcesi, S.;La Piana, R.;Fazzi, E.
aicardii - goutieres综合征（AGS）是一种常染色体隐性脑病，其特征是获得性小头畸形、脑钙化、脑白质营养不良、脑萎缩和脑脊液表现为慢性淋巴细胞增多和干扰素α (inf - α)升高。主要的神经外症状是冻疮样皮肤病变，通常在手指、脚趾和耳朵上。本综述是基于对1984年以来关于AGS的已发表文献（特别是最近的论文）的检索，以及作者与国际阿卡迪-古蒂耶综合征协会（IAGSA）合作所获得的知识和经验。AGS可被误认为先天性感染，其主要体征（nf - α水平升高、基底神经节钙化）在疾病的不同阶段的诊断意义是不同的。目前，我们知道有四种基因如果发生突变，就会导致AGS，但至少还有一种基因被认为是存在的。这些基因参与DNA损伤反应，其缺陷可能引发不适当的先天免疫反应，引发inf - α分泌增加，最终导致该疾病的主要特征。由于缺乏广泛的、长期的神经放射学随访研究，AGS的自然史尚未得到明确的描述。此外，目前还不清楚先天免疫系统是如何被激活的，是什么触发了这种疾病的发作，以及为什么它会在几个月后“耗尽”。在疾病的活跃期进行免疫抑制治疗似乎不会对临床病程产生任何真正的改变，但需要更多的数据。目前的研究旨在阐明AGS发病机制的分子机制，并建立保留核酸激活免疫系统的确切途径。这一知识有助于制定治疗策略。
Aicardi-Goutieres syndrome (AGS) is an autosomal recessive encephalopathy characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, cerebral atrophy and cerebrospinal fluid findings of chronic lymphocytosis and raised interferon-alpha (INF-alpha). The main extraneurological symptoms are chilblain-like skin lesions, usually on the fingers, toes and ears.This review is based on a search of the published literature on AGS from 1984 onwards (particularly the most recent papers) and on knowledge and experience gained through the authors' work with the International Aicardi-Goutieres Syndrome Association (IAGSA).It is accepted that AGS can be mistaken for a congenital infection and that the diagnostic significance of its cardinal signs (raised INF-alpha levels, basal ganglia calcifications) is different in different stages of the disease. Currently, we know of four genes that, if mutated, can give rise to AGS, but at least one other gene is believed to exist. These genes are involved in the DNA damage response, a defect of which could provoke an inappropriate innate immune response, triggering increased secretion of INF-alpha, ultimately responsible for the main features of the disease.The natural history of AGS has not yet been definitively described given the lack of extensive, long-term neuroradiological follow-up studies. Furthermore, it is not yet clearly understood how the innate immune system is activated, what triggers the onset of the disease or why it tends to 'burn out' after several months. Immunosuppressive therapy in the active stage of the disease does not seem to produce any real change in the clinical course, but more data are needed.Current studies aim to clarify the molecular mechanisms underlying the pathogenesis of AGS and to establish the exact pathway by which retained nucleic acids activate the immune system. This knowledge could allow the development of therapeutic strategies.