Introduction We present the case of a woman with an 8 year history of slowly progressive cognitive dysfunction and gait disturbance, and a diagnosis of vanishing white matter disease (VWMD).

Case The patient struggled at work as an accountant, her hand writing became illegible, she had difficulty judging distances when driving and she had developed gait instability, slowing and falls. Her past medical history was unremarkable save for premature menopause at 35. Examination showed marked cognitive impairment ACE-R 59/100 (attention and orientation – 13/18, memory – 16/26, fluency – 1/14, language – 21/26, visuospatial – 8/16), reduced dexterity of hands, left upper limb ataxia and high- level gait dysfunction. MRI brain showed leukodystrophy with frontal predominance. Relevant investigations – white cell enzymes, very long chain fatty acids, phytanic acid, CSF were normal. In view of the clinical and radiological features genetic testing with leukodystrophy panel was performed which revealed homozygous eukaryotic translation initiation factor B3 (EIF2B3) mutation (p.Ala87Val variant). Adult onset leukodystrophies are rare genetic metabolic disorders of the glial cells. The white matter (WM) degeneration causes disruption of distributed neural networks resulting in variable constellation of cognitive dysfunction, ataxia, pyramidal and extrapyramidal signs. The clinical and radiological phenotypes overlap and there are up to 60 genes that account for adult onset leukodystrophy, which makes diagnosis challenging. Vanishing white matter disease due to EIF2B gene mutation are a group of disorders that result from mutation of any of the EIF2B subunits (1 to 5). Two thirds have associated premature ovarian failure. MRI shows confluent WM T2 high signal, subcortical U Fibre sparing, periventricular WM rarefaction and cerebral atrophy. Management is symptomatic.

Conclusion Adult onset VWMD is a rare and devastating condition. When evaluating these patients targeted gene testing guided by clinical and radiological phenotype is likely to provide the highest diagnostic yield. Establishing the diagnosis is important as it has implications on future generations.