Abstract:
Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy classically characterized by early onset of severe neurologic injury with basal ganglia calcifications, white matter abnormalities, and progressive cerebral atrophy, along with lymphocytosis and raised interferon alpha (INFα) in the cerebrospinal fluid (CSF). Here, we report a 31/2 year-old patient born with prenatal onset AGS, first manifesting as intra-uterine growth retardation. Cranial ultrasonography and cerebral MRI revealed ventriculomegaly and periventricular and basal ganglia calcifications, along with cerebral atrophy. Perinatal infections and known metabolic disorders were excluded. Both CSF lymphocytosis and raised INFα were present. Molecular analysis disclosed two already described compound heterozygous pathogenic variants in TREX1 (c. 309dup, p.(Thr104Hisfs*53) and c. 506G > A, p.(Arg169His)). The evolution was marked by severe global developmental delay with progressive microcephaly. Promptly, the patient developed irritability, quadri-paretic dyskinetic movements, and subsequently tonic seizures. Sensorineural hearing loss was detected as well as glaucoma. Initially, he was symptomatically treated with trihexyphenidyl followed by levetiracetam and topiramate. At age 22 months, baricitinib (0.4 mg/kg/day) was introduced, leading to normal serum INFα levels. Clinically, dyskinetic movements significantly decreased as well as irritability and sleep disturbance. We confirmed that baricitinib was a useful treatment with no major side effect.
摘要:
Aicardi-Goutières综合征(AGS)是一种遗传性干扰素病,其典型特征是早期出现严重的神经系统损伤并伴有基底神经节钙化,白质异常,进行性脑萎缩,伴随淋巴细胞增多和脑脊液(CSF)中干扰素α(INFα)升高。这里,我们报告了一名31/2岁的产前发病AGS患者,首先表现为子宫内生长迟缓。头颅超声和脑MRI显示脑室扩大和脑室周围和基底节钙化,伴随着脑萎缩.围产期感染和已知的代谢紊乱被排除。同时存在CSF淋巴细胞增多和INFα升高。分子分析公开了TREX1中已经描述的两种复合杂合致病变体(c。309dup,p.(Thr104Hisfs*53)和c。506G>A,p.(Arg169His)。进化的特点是严重的全球发育迟缓和进行性小头畸形。及时,病人变得易怒,四肢运动障碍运动,以及随后的强直性癫痫发作。检测到感觉神经性听力损失以及青光眼。最初,他的症状是用三己苯基治疗,然后是左乙拉西坦和托吡酯。在22个月大的时候,引入baricitinib(0.4mg/kg/天),导致血清INFα水平正常。临床上,运动障碍明显减少,烦躁和睡眠障碍。我们证实baricitinib是一种有用的治疗方法,没有严重的副作用。