Adult-onset vanishing white matter disease with the EIF2B2 gene mutation presenting as menometrorrhagia

Abstract Background 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. Case presentation 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. Conclusions 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.