Kanmaz Seda, Simsek Erdem, Yilmaz Sanem, Durmaz Asude, Serin Hepsen Mine, Gokben Sarenur
Division of Child Neurology, Department of Pediatrics, Ege University Medical School, Izmir, Turkey.
Department of Medical Genetics, Ege University Medical School, Izmir, Turkey.
Acta Neurol Belg. 2023 Feb;123(1):121-127. doi: 10.1007/s13760-021-01700-7. Epub 2021 May 17.
Cerebral folate deficiency (CFD) syndrome is a rare treatable neurometabolic disorder with low levels of the active form of folaten in cerebrospinal fluid (CSF) arising from different causes such as FOLR1 gene mutations or autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus. It is characterized by late infantile onset refractory seizures, ataxia, movement disorder, and unexplained global developmental delay. Here, we report a patient diagnosed with autistic spectrum disorder, followed by refractory myoclonic-atonic seizures, ataxia, and loss of motor skills over time. A homozygous missense (c.665A > G) mutation in FOLR1 gene and extremely low CSF 5-methyltetrahydrofolate level led to the diagnosis of CFD. Although she was initiated on combined oral and intravenous high doses of folinic acid treatment at 6 years of age, mild improvement was achieved in terms of epileptic seizures and motor skills. It is important that CFD should be kept in mind in cases with refractory myoclonic-atonic seizure and folinic acid treatment should be started as soon as possible.
脑叶酸缺乏(CFD)综合征是一种罕见的可治疗的神经代谢障碍,由于不同原因,如FOLR1基因突变或针对叶酸受体-α(FR)蛋白的自身抗体,导致脑脊液(CSF)中活性叶酸水平降低,这些抗体可阻断叶酸通过脉络丛的转运。其特征为婴儿晚期起病的难治性癫痫发作、共济失调、运动障碍以及不明原因的全面发育迟缓。在此,我们报告一名患者,最初被诊断为自闭症谱系障碍,随后出现难治性肌阵挛-失张力发作、共济失调,并随着时间推移出现运动技能丧失。FOLR1基因的纯合错义突变(c.665A>G)以及极低的脑脊液5-甲基四氢叶酸水平导致了CFD的诊断。尽管她在6岁时开始接受口服和静脉联合高剂量亚叶酸治疗,但癫痫发作和运动技能方面仅取得了轻微改善。对于难治性肌阵挛-失张力发作的病例,应考虑到CFD,并且应尽快开始亚叶酸治疗,这一点很重要。