Innovation center for neurological disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
BMC Neurol. 2019 Aug 22;19(1):203. doi: 10.1186/s12883-019-1429-9.
Vanishing white matter disease (VWMD) is one of the most prevalent inherited leukoencephalopathies, which generally presents in childhood as a progressive disorder while less beginning in adulthood. The present report describes the clinical, neuroimaging, and genetic findings of a female patient with adult-onset VWMD. In addition, to provide a clearer delineation of the clinical and genetic characteristics of female adult-onset VWMD patients, 32 genetically confirmed female adult-onset EIF2B-mutated cases are summarized.
The patient described here suffered from long-term menometrorrhagia prior to manifesting progressive neurological impairments that included tremors, bilateral pyramidal tract injury, cerebellar ataxia, and dementia. To the best of our knowledge, this is the first female patient with adult-onset VWMD suffering from long-term menometrorrhagia attributed to the c.254 T > A and c.496A > G mutations in the EIF2B2 gene; the c.496A > G mutation has not been reported in previous studies. The patient also exhibited metabolic dysfunction. The present findings widen the spectrum of phenotypic heterogeneity observed in VWMD patients.
The present report summarizes 33 female patients with adult-onset VWMD to provide an overview of the clinical and genetic characteristics of this disorder and ovarioleukodystrophy. The mean age of clinical onset in female patients with adult-onset VWMD was 36.8 years and the neurological symptoms primarily included motor and cognitive dysfunction such as paraparesis, cerebellar ataxia, and executive deficits. In addition, ovarian failure occurred in all of these female patients and usually preceded the neurological symptoms. Furthermore, several patients also suffered from metabolic dysfunction. All 33 patients had mutations on EIF2B1-5, and of these, the c.338 G > A mutation in the EIF2B5 gene (p.Arg113His) was the most common. These findings suggest that clinicians should be aware of adult-onset forms of VWMD as well as its typical magnetic resonance imaging (MRI) and clinical characteristics although this pathology is usually recognized as a pediatric disorder. No curative treatment is presently available, and thus early recognition is important to prevent triggering events and to allow for genetic counseling.
脑白质消融症（VWMD）是最常见的遗传性脑白质病之一，通常在儿童期表现为进行性疾病，而在成年期发病较少。本报告描述了一位成年起病 VWMD 女性患者的临床、神经影像学和遗传学发现。此外，为了更清楚地阐明女性成年起病 VWMD 患者的临床和遗传特征，总结了 32 例经基因证实的女性成年起病 EIF2B 突变病例。
本文描述的患者在出现进行性神经功能障碍之前，长期存在月经过多，包括震颤、双侧锥体束损伤、小脑共济失调和痴呆。据我们所知，这是首例成年起病 VWMD 女性患者，因 EIF2B2 基因 c.254T> A 和 c.496A> G 突变而长期月经过多；以前的研究中未报道过 c.496A> G 突变。患者还表现出代谢功能障碍。本研究结果拓宽了 VWMD 患者表型异质性的范围。
本报告总结了 33 例女性成年起病 VWMD 患者，以概述该疾病和卵巢脑白质营养不良的临床和遗传特征。女性成年起病 VWMD 患者的平均发病年龄为 36.8 岁，神经症状主要包括运动和认知功能障碍，如截瘫、小脑共济失调和执行功能缺陷。此外，所有这些女性患者均出现卵巢功能衰竭，且通常早于神经症状。此外，一些患者还患有代谢功能障碍。所有 33 例患者均有 EIF2B1-5 基因突变，其中 EIF2B5 基因 c.338G> A 突变（p.Arg113His）最为常见。这些发现表明，尽管这种病理通常被认为是儿科疾病，但临床医生应该意识到 VWMD 的成年起病形式及其典型的磁共振成像（MRI）和临床特征。目前尚无治愈方法，因此早期识别很重要，可以预防触发事件并进行遗传咨询。
