Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency
Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency
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DOI：
10.1016/j.braindev.2016.09.011
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发表时间：
2017-03-01
影响因子：
1.7
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Yu;Tohyama, Jun;Matsumoto, Naomichi
叶酸受体1基因（FOLR 1）突变引起的脑叶酸缺乏症是一种由脑特异性叶酸转运缺陷引起的常染色体隐性遗传疾病。其特征是婴儿期发病晚，严重的精神退化，癫痫和脑白质营养不良。我们描述了一个近亲女孩表现出严重的发展倒退，顽固性癫痫，多发性神经病，和深刻的髓鞘形成不足与皮质参与。磁共振成像显示皮质紊乱除了深刻的髓鞘形成和小脑萎缩。神经传导研究发现轴突变性和脱髓鞘的功能。脑叶酸缺乏症的诊断通过FOLR 1中的纯合c.466T>G（p.W156G）突变以及极低的脑脊液5-甲基四氢叶酸水平得到证实。她的症状，神经放射学检查结果，和多发性神经病缓解口服亚叶酸治疗联合静脉和肌肉注射治疗。我们的病人显示，亚叶酸治疗可以改善临床症状，白色物质障碍，皮质损伤，和周围神经病变的脑叶酸缺乏引起的FOLR 1突变。重要的是要认识到这些临床症状，并作出准确的诊断早期，因为脑叶酸缺乏症是可以治疗的。(C)2016日本儿童神经病学学会。Elsevier B. V.出版，保留所有权利。
Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy. Nerve conduction studies revealed both axonal degeneration and demyelinating features. A diagnosis of cerebral folate deficiency was confirmed by a homozygous c.466T>G (p.W156G) mutation in FOLR1, coupled with extremely low cerebrospinal fluid levels of 5-methyltetrahydrofolate. Her symptoms, neuroradiological findings, and polyneuropathy were alleviated by oral folinic acid treatment in conjunction with intravenous and intramuscular administration therapy. Our patient shows that folinic acid therapy can ameliorate the clinical symptoms, white matter disturbances, cortical insults, and peripheral neuropathy of cerebral folate deficiency caused by FOLR1 mutation. It is important to recognize these clinical symptoms and make a precise diagnosis early on, because cerebral folate deficiency is treatable. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.