Leukodystrophy with premature ovarian failure: think on vanishing white matter disease (VWMD)

Leucodistrofia com falência ovariana prematura: pense na doença da substância branca evanescente

A 46-year-old female presented progressive hand tremor at age of 8, associated to cognitive and motor deterioration. She developed incapacitating head tremor and was wheelchair-bound 12 years after onset. Premature ovarian failure (POF) occurred at 27-year-old. In the last 3 years, head tremor became less intense, but she remained with horizontal bidireccional nistagmus.

Vanishing white matter disease (VWMD) is an autosomal recessive disorder characterized by cerebellar ataxia, spasticity, and cognitive impairment^1,2. Brain MRI discloses symmetric and diffuse white matter lesions (figure). VWMD manifests from infancy to adulthood; in female, POF may occur³. It is caused by mutations in both alleles of one of five genes coding for subunits of eukaryotic translation initiation factor 2B.

Figure
(A, B, and C) T2-weighted acquisition showing diffuse abnormal white matter signal, with intensity close to of the cerebrospinal fluid; and (D) Fluid-attenuated inversion recovery (FLAIR), showing diffuse hyperintensity in white matter.

References

• ¹
  Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology. 1998;51(2):540-7.
• ²
  Costello DJ, Eichler AF, Eichler FS. Leukodystrophies: classification, diagnosis, and treatment. Neurologist. 2009;15(6):319-28. http://dx.doi.org/10.1097/NRL.0b013e3181b287c8
  » https://doi.org/10.1097/NRL.0b013e3181b287c8
• ³
  Schiffmann R, Tedeschi G, Kinkel RP, Trapp BD, Frank JA, Kaneski CR et al. Leukodystrophy in patients with ovarian dysgenesis. Ann Neurol. 1997;41(5):654-61.

Publication Dates

• Publication in this collection
  Jan 2015

History

• Received
  04 Aug 2014
• Reviewed
  02 Sept 2014
• Accepted
  22 Sept 2014