背景:Aicardi-Gouteres综合征(AGS)是一种以早期发病为特征的单基因干扰素病,皮肤失调(冻疮损伤),大脑,和免疫系统(发烧,肝肿大,青光眼,关节炎,肌炎,和自身免疫活动)。这种疾病看起来像TORCH(弓形虫病,Others,风疹,巨细胞病毒,疱疹)感染早发性脑病,导致严重的神经心理残疾。
方法:一名6岁女孩一直患有全身性癫痫,发烧发作,严重的精神运动发育迟缓,从她生命的第一年起就出现了痉挛性四轻瘫。她的两个哥哥在很小的时候就死于疑似婴儿脑瘫(ICP)。其他兄弟姐妹(弟弟和两个姐姐)和他们的父母一样健康。该女孩在5.5岁时被诊断出患有青少年皮肌炎。基底神经节,脑室周围,和小脑钙化;call体发育不全;在CT上检测到脑白质营养不良。IFN-I评分比正常人高12倍。在SAMHD1基因的外显子4中以纯合状态检测到先前未描述的核苷酸变体c.434G>C(chr20:36935104C>G;NM_015474),导致氨基酸取代p.R145P诊断为Aicardi-Goutières综合征5。她的治疗包括皮质类固醇,甲氨蝶呤,和托法替尼5毫克,每天两次,它有助于改善健康。随后的脑部CT描绘了先前发现的变化,没有钙化扩散的迹象。
结论:AGS的早期诊断非常重要,因为它可以及时开始治疗。及时治疗,作为回报,可以帮助避免终末器官损伤的发展/进展,包括严重的神经系统并发症和早期死亡。有必要在神经学家中传播有关AGS的信息,新生儿学家,传染病专家,和儿科医生。需要多学科的团队方法。
BACKGROUND: Aicardi-Gouteres syndrome (AGS) is a monogenic
interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability.
METHODS: A six-year-old girl has been suffering from generalized seizures, fever episodes, severe psychomotor development delay, and spastic tetraparesis since the first year of her life. Her two elder brothers died at a young age from suspected infantile cerebral palsy (ICP). Other siblings (younger brother and two elder sisters) are as healthy as their parents. The girl was diagnosed with juvenile dermatomyositis at 5.5 years. Basal ganglia, periventricular, and cerebellum calcifications; hypoplasia of the corpus callosum; and leukodystrophy were detected on CT. The IFN-I score was 12 times higher than normal. The previously not described nucleotide variant c.434G > C (chr 20:36935104C > G; NM_015474) was detected in exon 4 of the SAMHD1 gene in the homozygous state, leading to amino acid substitution p.R145P. Aicardi-Goutières syndrome 5 was diagnosed. Her treatment included corticosteroids, methotrexate, and tofacitinib 5 mg twice a day and it contributed to health improvements. The following brain CT depicted the previously discovered changes without the sign of calcification spreading.
CONCLUSIONS: Early diagnosis of AGS is highly important as it allows starting treatment in a timely manner. Timely treatment, in return, can help avoid the development/progression of end-organ damage, including severe neurological complications and early death. It is necessary to spread information about AGS among neurologists, neonatologists, infectious disease specialists, and pediatricians. A multidisciplinary team approach is required.