Leukoencephalopathy with vanishing white matter

A rare genetic disorder affecting the central nervous system

Leukoencephalopathy with vanishing white matter
Autosomal recessive - en.svg
This condition is inherited in an autosomal recessive manner
Synonyms	Childhood ataxia with central nervous system hypomyelinization, Vanishing white matter leukodystrophy, Cree leukoencephalopathy, Vanishing white matter leukodystrophy with ovarian failure, Myelinopathia centralis diffusa
Specialty	Neurology, Medical genetics
Symptoms	Ataxia, spasticity, optic atrophy, epilepsy, coma, behavioral changes
Complications	Loss of motor function, premature ovarian failure, coma, death
Usual onset	Typically childhood, can occur in infancy or adulthood
Duration	Progressive
Types	Based on age of onset (infantile, childhood, juvenile, adult)
Causes	Mutations in EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5 genes
Risk factors	Inherited autosomal recessive trait
Diagnosis	MRI, genetic testing, neurological examination
Differential diagnosis	Multiple sclerosis, other leukodystrophies
Prevention	None
Treatment	Supportive care, symptom management, avoidance of stressors
Medication	Anticonvulsants for seizures, supportive treatments
Prognosis	Poor, especially with early onset
Frequency	Rare
Deaths	Common in severe forms

File:EIF2regulation.jpg

Overview of eIF2 and eIF2B's purpose in cells

Leukoencephalopathy with vanishing white matter (VWM), also known as vanishing white matter disease, is a rare genetic disorder that primarily affects the central nervous system (CNS). It is characterized by the progressive loss of white matter in the brain, leading to a variety of neurological symptoms.

Pathophysiology

Leukoencephalopathy with vanishing white matter 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. The eIF2B complex is crucial for the regulation of protein synthesis, particularly under conditions of cellular stress. Mutations in these genes disrupt normal protein synthesis, leading to the degeneration of white matter in the brain.

The disease is characterized by the progressive disappearance of white matter, which is replaced by cerebrospinal fluid. This process is visible on magnetic resonance imaging (MRI) scans, which show a characteristic pattern of white matter loss.

Clinical Presentation

The clinical presentation of VWM can vary widely, but it typically includes:

• Ataxia
• Spasticity
• Seizures
• Optic atrophy
• Cognitive decline

Symptoms often begin in early childhood, but the age of onset can range from infancy to adulthood. The disease is progressive, and stressors such as fever, minor head trauma, or infections can exacerbate the symptoms.

Diagnosis

Diagnosis of leukoencephalopathy with vanishing white matter is based on clinical evaluation, MRI findings, and genetic testing. MRI scans reveal the characteristic pattern of white matter loss, while genetic testing can confirm mutations in the eIF2B genes.

Management

There is currently no cure for VWM, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. This may include:

• Physical therapy to manage spasticity and improve mobility
• Anticonvulsant medications to control seizures
• Supportive care for cognitive and developmental issues

Avoidance of stressors that can exacerbate the disease is also crucial.

Prognosis

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

Related pages

• Leukoencephalopathy
• White matter disease
• Genetic disorders
• Central nervous system disorders