Vanishing White Matter Disease

What is Vanishing White Matter Disease?

Vanishing White Matter Disease (VWM) is inherited in an autosomal recessive manner, meaning that it is a disease that can run in a family. Symptoms generally appear in young children, who may appear to be developing fairly normally. However, it has been shown that it can begin at or shortly after birth, as well as in adulthood. A striking feature of the disease is that the symptoms generally worsen slowly, yet there can be episodes of rapid deterioration that follow an infection or head trauma. The patient may have a partial recovery following these episodes, or the episode may lead to coma and death.

What causes VWM?

VWM is caused by mutations in one of the five genes that are collectively called eIF2B or eukaryotic initiation factor 2B. This gene is necessary to properly make proteins in the body. It is so important that no one can be born with a complete absence of this gene. VWM is caused by changes in the gene that reduces the function of eIF2B. This reduction in function becomes a particular problem during episodes of fever, infection, or head traumas, and deterioration accelerates following such episodes.

How is VWM diagnosed?

VWM is diagnosed on the basis of the clinical symptoms in combination with the results of an MRI. In addition, because the specific genetic defect that causes VWM is known, DNA techniques can also be used to confirm VWM.

What are the symptoms of VWM?

Generally, a child with VWM will appear relatively normal at birth, though he/she may have slightly delayed psychomotor development. Symptoms may appear beginning in late infancy or early childhood and can vary widely from case to case. These are possible symptoms:

  • Neurological deterioration
  • Febrile episodes: episodes of fever. In VWM, this is associated with worsening of symptoms, drowsiness, or coma.
  • Spasticity: tending to suffer spasms or involuntary contractions of muscles. Muscles are abnormally stiff, and movement is restricted.
  • Lethargy: abnormal drowsiness and indifference to environmental stimuli
  • Coma
  • Death: will generally occur after a variable period, ranging from a few years to a few decades. Normally, death results from an episode of fever and/or coma.
  • Ovary dysgenesis: defective development of the ovaries.
  • Cerebellar ataxia: loss of muscle coordination as a result of abnormal functioning of the cerebellum.
  • Optic atrophy: an abnormality of the eyes.
  • Seizures
  • Mental impairment: may be present, though generally less severe than the motor dysfunction

The motor difficulties of VWM are progressive, but the progression is often stepwise in association with fever or injuries. Prolonged periods of stability or even transient mild improvements lasting years are common. Most patients develop seizures (epilepsy) late in the illness, and they are easy to control. Life expectancy is reduced, though patients can live into their second or third decades.

What is the treatment for VWM?

There is no cure for VWM. Treatment is supportive.

How is scientific research on VWM progressing toward improved diagnosis or treatment?

The identification of the genetic basis of VWM was a great step forward. It allows scientists to develop genetic testing methods for diagnosing VWM. If you know that the disease runs in your family, you can talk to a genetic counselor about the option of prenatal testing, as well as testing of family members, so that everyone can discover if they are carriers of the disease.

Other Clinical Names for Vanishing White Matter Disease

Other clinical names of Vanishing White Matter Disease include:

  • Childhood Ataxia with diffuse CNS Hypomyelination (CACH)
  • Vanishing White Matter Leukodystrophy
  • Cree Leukoencephalopathy
  • Vanishing White Matter Leukodystrophy with Ovarian Failure