进行性线粒体脑病表现为发育迟缓,回归,癫痫,肌阵鸣,肌张力障碍,由于NARS2中的新型复合杂合变体而引起的痉挛尚未被报道。患者是一名3.5岁的女性,精神运动发育正常,直到她在4.5个月大时首次出现全身性癫痫持续状态。控制癫痫发作后,全身肌阵鸣和精神运动消退变得明显。尽管使用了多种抗癫痫药物,但她还患有另外两种癫痫状态,癫痫发作控制仍然不足。神经系统检查显示广泛性张力减退,不协调,不稳定的眼神接触,流口水,张开嘴,肌阵鸣,周期性斜颈,和脚踝收缩。脑MRI显示,由于双侧弥漫性皮质和皮质下萎缩以及不完全的髓鞘形成,导致脑积水。12月龄时的基因检测显示NARS2中的复合杂合变体chr11:78204182C>T和chr11:78282446A>AG。尽管有抗癫痫药物,线粒体鸡尾酒,和大麻二酚,该疾病进展为顽固性癫痫发作和严重的四逆性。总之,该病例表明,NARS2中的复合杂合变体可以在表型上仅在患有难治性癫痫的大脑中表现出来,肌阵鸣,发育迟缓,回归,低张力,脑萎缩,和髓鞘不足,其次是四肌张力障碍和肌张力障碍。
Progressive
mitochondrial encephalopathy manifesting as developmental delay, regression, epilepsy, myoclonus, dystonia, and spasticity due to a novel compound heterozygous variant in NARS2 has not been reported. The patient is a 3.5-year-old female with normal psychomotor development until she experienced her first generalized status epilepticus at 4.5 months of age. After seizure control, generalized myoclonus and psychomotor regression became evident. She suffered from two other epileptic states and seizure control remained inadequate despite the use of multiple anti-seizure drugs. Neurologic examination revealed generalized hypotonia, discoordination, unstable eye contact, drooling, open mouth, myoclonus, periodic torticollis, and ankle contractions. Cerebral MRI revealed hydrocephalus ex vacuo due to diffuse cortical and subcortical atrophy bilaterally and incomplete myelination. Genetic testing at 12 months of age revealed the compound heterozygous variants chr11: 78204182C>T and chr11: 78282446A>AG in NARS2. Despite anti-seizure drugs,
mitochondrial cocktail, and cannabidiol, the disease progressed to intractable seizures and severe tetraspasticity. In summary, this
case demonstrates that compound heterozygous variants in NARS2 can phenotypically manifest exclusively in the brain with intractable epilepsy, myoclonus, developmental delay, regression, hypotonia, cerebral atrophy, and hypomyelination, followed by tetraspasticity and dystonia.