Differential Diagnosis:

Leukodystrophy (diseases of abnormal myelin formation or metabolism)

- Adrenoleukodystrophy

- Alexander disease

- Pelizaeus-Merzbacher disease

- Krabbe disease

- Canavan disease

- Leukoencephalopathy with vanishing white matter

- Metachromatic leukoencephalopathy

- Retinal vasculopathy with cerebral leukodystrophy

- And more!

Diagnosis and Discussion:

Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive condition caused by mutations in EIF2B. This degenerative condition is slowly progressive with episodes of acute worsening of symptoms. These episodes can be triggered by head injury, fever, and strong emotions.

Disease onset can occur in childhood or adulthood, with symptoms including ataxia, spasticity, epilepsy, migraine, and cognitive changes. Premature ovarian failure or amenorrhea can occur in women. MRI is useful for diagnosis, and shows diffuse, symmetric changes of cerebral white matter, with sparing of the U-fibers, corpus callosum, anterior commissure, and internal capsule. Eventually cystic degeneration of white matter occurs.

Tissue examination shows cerebral atrophy with large ventricles, discolored or cystic subcortical white matter, and relative sparing of U-fibers, corpus callosum, anterior commissure, and internal capsule. Histology is notable for pallor of the affected white matter, with numerous oligodendroglial precursor cells and minimal inflammation.