What is Vanishing White Matter?
Vanishing white matter (VWM) is a disorder in which nerve tissue in the brain and spinal cord degrades over time. The condition is sometimes called leukoencephalopathy with vanishing white matter or childhood ataxia with diffuse central nervous system hypomyelination.
VWM most often first appears in early childhood, between the ages of one and five, but it can occur at any stage of life. Symptoms of the disorder and prognosis vary depending on the age of onset.
People with VWM often experience alternating periods of relatively stable symptoms and rapid worsening of symptoms. Both initial symptoms and periods of rapid progression may be triggered by external events such as an infection or a minor head injury.
Types of VWM
VWM is classified into different types according to the age of onset. Types of the disorder include:
- Antenatal onset. This type of VWM begins during pregnancy. Unfortunately, children with this form of VWM often don’t survive more than a few months after birth.
- Infantile onset. This form appears in the first few months of life, and survival past two years is unlikely.
- Early childhood onset. This is the most common type of VWM. Symptoms appear between the ages of one and five after a period of apparently normal development.
- Juvenile onset. This type emerges in late childhood or adolescence and typically progresses more slowly than earlier-onset forms.
- Adult onset. In contrast to other types of VWM, initial symptoms of this form are usually behavioral changes or cognitive decline.
Symptoms of VWM
Symptoms of VWM vary depending on the age of onset and progressively worsen over time. Common symptoms include:
- Muscle stiffness
- Problems with coordination (ataxia)
- Deterioration of the optic nerves
- Abnormal development of ovaries in females
- Sleepiness or lethargy
- Behavioral changes
- Mental decline
What Causes Vanishing White Matter?
VWM is caused by abnormal changes (mutations) in five different genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5). These genes carry instructions for making a protein crucial to producing other proteins vital for cell function. When these genes malfunction, the body’s cells cannot function properly and may die when they’re subjected to stress.
Specific cells in the central nervous system called white matter are susceptible to stress and are significantly impacted by the gene mutations that cause VWM. As a result, these cells may be vulnerable to stress caused by infections or injury. This may explain why stressful events often trigger the progression of VWM.
Is Vanishing White Matter Hereditary?
VWM is an inherited disorder. The mutations that cause it can be passed from parents to their children in an autosomal recessive pattern. This means that a child must inherit two copies of the disorder-causing gene mutation, one from each parent, to develop the condition. A parent who carries only one copy of the mutation will usually show no symptoms but may pass the mutation to their children. Two parents who each carry the mutation have a 25 percent chance of having an affected child with each pregnancy. Fifty percent of their pregnancies will produce a carrier child. Twenty-five percent of the time, their child will not inherit a mutated gene, meaning they will not have the disorder or be able to pass on the mutation to their children.
How Is Vanishing White Matter Detected?
In juvenile-onset VWM, the first symptoms are typically muscle stiffness, problems with coordination, and other motor difficulties. Cognitive decline and other mental symptoms are uncommon in the early stages of early-onset VWM, but they are often the first symptoms to appear in the adult-onset form.
In some cases, magnetic resonance imaging (MRI) may detect the brain deterioration characteristic of VWM before symptoms appear.
How Is Vanishing White Matter Diagnosed?
A doctor may suspect VWM when physical and neurological exams show the disorder’s symptoms, and other potential causes can be ruled out. The diagnostic process for VWM typically includes:
- Imaging scans such as magnetic resonance imaging (MRI) to look for abnormalities in the brain
- Genetic testing to look for disorder-causing mutations and confirm the diagnosis
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Vanishing White Matter Treated?
VWM has no cure, and no treatment will reverse the disorder’s symptoms. However, some treatments and therapies may help prevent periods of decline, and others may improve quality of life and prevent complications. Common treatments and therapies include:
- Anti-seizure medications
- Anti-fever medications
- Physical therapy
How Does Vanishing White Matter Progress?
Progression of VWM may vary depending on the age of onset, and some cases may experience a faster progression than others. Early-onset forms are typically the most severe, but most cases will eventually progress to significant disabilities and complications.
Long-term symptoms of VWM may include:
- Loss of ability to walk
- Loss of use of hands
- Loss of speech
- Loss of ability to swallow
- Vision impairment or blindness
How Is Vanishing White Matter Prevented?
There is no known way to prevent VWM when the disorder-causing gene mutations are present. However, avoidance of stressors may help to prevent periods of rapid progression. Preventative measures include:
- Vaccination against infections
- Administration of preventative antibiotics
- Use of fever-reducing medications whenever fever is present
- Avoidance of contact sports and other potential sources of injury
- Wearing a helmet while outside
- Avoidance of high-temperature environments
- Avoidance of stressful or frightening situations
Parents with a family history of the disorder or who have had another child with VWM are advised to consult a genetic counselor to assess their risk if they plan to have another child.
Vanishing White Matter Caregiver Tips
- Keep your child safe. VWM is one of the rare leukodystrophies that you can do something about. Follow your doctor’s advice about preventative measures, and act quickly whenever your child experiences a fever or infection.
- Remember that there is a community of people who know what you’re going through, and they can help. The United Leukodystrophy Foundation maintains a directory of resources for families living with VWM, including links to education, medical referrals, and financial assistance programs.
Some people with VWM also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with VWM:
- People with VWM may be at increased risk for mood disorders such as depression.
- Some people with VWM symptoms similar to those of schizophrenia, including hallucinations and delusions.
- People with VWM may be at increased risk of dementia.
Vanishing White Matter Brain Science
The EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5 genes each carry instructions for producing components of a protein called eIF2B.This protein works together with another protein (eIF2). Together, these two proteins regulate the process that allows cells to manufacture other proteins. The elF2B mutations interfere with this process and disrupt protein production inside cells, making the cells more vulnerable to damage and death, especially in times of stress.
VWM is a type of disorder called leukodystrophy. These disorders affect white matter cells, nerve cells in the brain and spinal cord covered with a fatty substance called myelin that protects them and allows them to communicate effectively with other nerve cells. White matter seems to be especially sensitive to the conditions produced by elF2B mutations, so the cells are more likely to die when they’re exposed to stressful conditions.
Vanishing White Matter Research
Title: Longitudinal Study of Neurodegenerative Disorders
Principal investigator: Maria L. Escolar, MD, MS
Children’s Hospital of Pittsburgh of UPMC
The purpose of this study is to understand the course of rare genetic disorders that affect the brain. In addition, this data is being analyzed to better understand the progression of rare neurodegenerative diseases and the effects of interventions.
Patients would be evaluated by a multidisciplinary team at specific time points every three months the first year, every six months the second year, and once a year thereafter.
Title: Natural History, Diagnosis, and Outcomes for Leukodystrophies
Contact: Josh Bonkowsky, MD, PhD
Primary Children’s Hospital
Salt Lake City, UT
This protocol aims to diagnose, care for, and understand the clinical histories and outcomes of people with leukodystrophies.
Inherited leukodystrophies affect close to 1 in 7500 children with mortality greater than 30%. Affected patients face additional serious medical complications, including epilepsy, developmental regression, and intellectual disabilities. Diagnosis is difficult and requires the assistance of a specialist. Finally, identifying treatments and improving outcomes is complex.
The Western Leukodystrophy Project, which is part of the University of Utah and Primary Children’s Hospital, and is a certified Leukodystrophy Care Network Center, provides a specialized resource for patients with leukodystrophies.
This clinical study assists with the diagnosis of leukodystrophies, suggesting treatment options and implementing care guidelines, and improving outcomes for all patients by understanding affected patients’ clinical histories and outcomes.