The objective of this case report was to describe the first report of FOLR1 variants associated with adult-onset paucisymptomatic leukoencephalopathy associated with cerebral folate deficiency (CFD).

Considering the patient's symptoms, a nonprogressive leukoencephalopathy was suspected. CSF 5-methyltetrahydrofolate levels were low (10 nmol/L, normal range 41–117). With no other identifiable causes, a genetic analysis was conducted, revealing a compound heterozygous FOLR1 variation (c.45G>T and c. 493+2T>C).

A 47-year-old man with a history of drug and alcohol abuse was admitted to the hospital for double vision and postural instability. MRI of the brain was performed, which showed bilateral leukoencephalopathy. Diffusion tensor imaging revealed a diffuse reduction in fractional anisotropy, suggesting microstructural changes. MRI of the brain and overall clinical picture were stable on subsequent serial examinations.

Scientific evidence supports the deleterious effect of c.45G>T and c.493+2T>C variations on the folate receptor-α (FRα) protein structure and function. The weakness of the expression and function of FRα without elimination of its function caused by specific compound heterozygous variations may explain the atypical features observed in our patient. Although rare, CFD should be considered in paucisymptomatic adult patients with stable diffuse MRI white matter changes.

本病例报告的目的是描述与成人发病的少症状白质脑病（与脑叶酸缺乏症 (CFD) 相关）相关的FOLR1变异的第一份报告。

考虑到患者的症状，怀疑患有非进行性白质脑病。脑脊液 5-甲基四氢叶酸水平较低（10 nmol/L，正常范围 41-117）。由于没有其他可识别的原因，进行了遗传分析，揭示了复合杂合FOLR1变异（c.45G>T 和 c.493+2T>C）。

一名47岁男子有吸毒和酗酒史，因复视和姿势不稳入院。进行了脑部 MRI 检查，结果显示双侧白质脑病。扩散张量成像显示分数各向异性的扩散减少，表明微观结构发生变化。在随后的系列检查中，大脑 MRI 和整体临床表现稳定。

科学证据支持 c.45G>T 和 c.493+2T>C 变异对叶酸受体-α (FRα) 蛋白质结构和功能的有害影响。由特定复合杂合变异引起的 FRα 表达和功能的弱化而不消除其功能可以解释在我们的患者中观察到的非典型特征。尽管罕见，但对于无症状且 MRI 白质弥漫性改变稳定的成年患者，应考虑 CFD。