General description

Vanishing white matter disease (VWMD), also known as childhood ataxia with central nervous system hypomyelination (CACH), is a rare autosomal recessive disorder caused by mutations in the eukaryotic translation initiation factor 2B (EIF2B) gene. The role of EIF2B in mRNA translation initiation is crucial, but why its mutations specifically lead to white matter degeneration remains unclear. The condition affects the brain's white matter, leading to progressive neurological symptoms such as cerebellar ataxia, spasticity, and pyramidal tract signs, usually appearing between the ages of 2 and 5. VWMD can manifest at any age, from infancy to adulthood, and is sometimes referred to as an EIF2B-related disorder.

The disease is characterized by slowly progressive neurological deterioration, with sudden symptom worsening triggered by stressors like infections, head trauma, or emotional stress. Though typically a childhood-onset condition, adult cases have been reported. The earlier the onset, the more severe the prognosis, with some cases resulting in death within a few years.

VWMD is the most common leukodystrophy in children, although its exact prevalence is unknown. VWMD can include ovarian dysfunction (termed ovarioleukodystrophy) in female patients, leading to premature ovarian failure. Other associated symptoms may include growth delays, cataracts, hepatosplenomegaly, pancreatitis, and kidney hypoplasia.

Radiographic features

MRI shows symmetric bilateral T2WI and FLAIR hyperintensity, primarily in the periventricular white matter of the frontal and parietal lobes. Additionally, MRI reveals water-like intensity in the affected white matter, suggesting cystic changes or cavity formation.

T2WI, FLAIR, and DWI also show hyperintensity in the cerebellar white matter, middle cerebellar peduncle, corpus callosum, posterior limb of the internal capsule, and the central tegmental tract of the pons.