Vanishing white matter disease

Vanishing White Matter Disease Vanishing White Matter Disease (VWMD), also known as Childhood Ataxia with Central Nervous System Hypomyelination (CACH), is a rare genetic disorder that affects the central nervous system. It is characterized by the progressive loss of white matter in the brain, leading to a variety of neurological symptoms.

Etiology

VWMD is caused by mutations in any of the five genes encoding the subunits of the eukaryotic translation initiation factor 2B (eIF2B). These genes are EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5. Mutations in these genes disrupt the normal function of eIF2B, which is crucial for protein synthesis and cellular stress response.

Pathophysiology

The disease primarily affects the white matter of the brain, which consists of myelinated nerve fibers. The myelin sheath is essential for the proper transmission of nerve impulses. In VWMD, the myelin sheath deteriorates, leading to the "vanishing" appearance of white matter on MRI scans. This demyelination process is progressive and results in neurological decline.

Clinical Presentation

Symptoms of VWMD can vary widely but often include:

• Ataxia (lack of voluntary coordination of muscle movements)
• Spasticity (muscle stiffness)
• Seizures
• Optic atrophy (damage to the optic nerve)
• Cognitive decline

The onset of symptoms can occur at any age, from early childhood to adulthood, but most commonly begins in childhood.

Diagnosis

Diagnosis of VWMD is based on clinical evaluation, MRI findings, and genetic testing. MRI typically shows a characteristic pattern of white matter loss. Genetic testing can confirm mutations in the eIF2B genes.

Management

Currently, there is no cure for VWMD. Management focuses on symptomatic treatment and supportive care. This may include physical therapy, occupational therapy, and medications to manage symptoms such as seizures and spasticity.

Prognosis

The prognosis for individuals with VWMD varies depending on the age of onset and the severity of symptoms. Early-onset cases tend to have a more rapid progression and poorer prognosis, while later-onset cases may progress more slowly.

Research and Future Directions

Research is ongoing to better understand the molecular mechanisms of VWMD and to develop potential therapies. Gene therapy and other novel approaches are being explored as potential treatments.

See Also

• Leukodystrophy
• Myelin
• Genetic disorders
• van der Knaap, M. S., et al. "Vanishing white matter disease: a review with focus on its genetics." *Neurology* 71.10 (2008): 787-793.
• Bugiani, M., et al. "Vanishing white matter disease: a review of clinical and pathological features." *Journal of Neuropathology & Experimental Neurology* 69.8 (2010): 751-758.

NIH genetic and rare disease info

• NIH info on Vanishing white matter disease

Vanishing white matter disease is a rare disease.