PDF(Pubmed)
Abstract：
UNASSIGNED: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy.
UNASSIGNED: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable.
UNASSIGNED: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations.
UNASSIGNED: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable.
UNASSIGNED: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations.
摘要：
未经证实：新发难治性癫痫持续状态(NORSE)与高发病率和高死亡率相关。尽管进行了大量的工作，50%的受影响个体的潜在病因仍然未知.线粒体疾病是NORSE的罕见原因。据报道，FASTKD2的双等位基因变异是婴儿脑肌病伴难治性癫痫的原因。
未经批准：在研究中，我们报告了一个以前健康的14岁孩子，呈有NORSE的纯合FASTKD2变体。在7年的无癫痫发作期之后，他经历了另一种超难治性SE，随后发展为耐药性局灶性癫痫，轻度肌病,视神经萎缩,和离散的精神运动减慢。NORSE时的结构MRI显示右颞顶枕骨FLAIR高强度和弥散限制，在22岁时患有广泛的右半球萎缩。全外显子组测序揭示了一种新的纯合功能缺失变体[c。(1072C>T)；(1072C>T)][p。(Arg358Ter);(Arg358Ter)]在FASTKD2(NM_001136193)中,导致蛋白质编码区的提前终止密码子和FASTKD2的功能丧失。肌肉和皮肤成纤维细胞中的氧化磷酸化(OXPHOS)不显著。
UNASSIGNED：这是正常发育的青少年的第一例，在FASTKD2中出现新的纯合功能缺失变异，表现为NORSE。FASTKD2相关线粒体疾病的表型谱是异质性的，从认知发育正常的青少年复发性癫痫持续状态和难治性局灶性癫痫到严重形式的婴儿线粒体脑病。虽然线粒体疾病是NORSE的罕见原因，发病年龄小和多系统受累等临床特征应触发基因检测.早期诊断对于咨询和治疗考虑至关重要。
未经批准：在研究中，我们报告了一个以前健康的14岁孩子，呈有NORSE的纯合FASTKD2变体。在7年的无癫痫发作期之后，他经历了另一种超难治性SE，随后发展为耐药性局灶性癫痫，轻度肌病,视神经萎缩,和离散的精神运动减慢。NORSE时的结构MRI显示右颞顶枕骨FLAIR高强度和弥散限制，在22岁时患有广泛的右半球萎缩。全外显子组测序揭示了一种新的纯合功能缺失变体[c。(1072C>T)；(1072C>T)][p。(Arg358Ter);(Arg358Ter)]在FASTKD2(NM_001136193)中,导致蛋白质编码区的提前终止密码子和FASTKD2的功能丧失。肌肉和皮肤成纤维细胞中的氧化磷酸化(OXPHOS)不显著。
UNASSIGNED：这是正常发育的青少年的第一例，在FASTKD2中出现新的纯合功能缺失变异，表现为NORSE。FASTKD2相关线粒体疾病的表型谱是异质性的，从认知发育正常的青少年复发性癫痫持续状态和难治性局灶性癫痫到严重形式的婴儿线粒体脑病。虽然线粒体疾病是NORSE的罕见原因，发病年龄小和多系统受累等临床特征应触发基因检测.早期诊断对于咨询和治疗考虑至关重要。
