Leukoencephalopathy with Vanishing White Matter

Clinical Characteristics
Ocular Features: 

Optic atrophy is a common feature and blindness is often the result.

Systemic Features: 

Onset of symptoms may occur at any time from 1.5 years of age to adulthood.  Early psychomotor development may be normal but developmental milestones such as walking and crawling are often delayed.  Patients with a later onset often have a milder course.  Progression is chronic but often episodic with exacerbations following infection and blunt head trauma. Mental stress, even of a relatively minor nature such as fright, may likewise cause a worsening of symptoms.  Such episodes can lead to loss of consciousness or even coma.  Cerebellar ataxia and spasticity are common.  Epilepsy may occur but is uncommon.  Motor function is more severely impaired compared with mental deterioration.  The MRI reveals a diffuse leukoencephalopathy as well as focal and cystic degeneration of white matter which may be present before the onset of symptoms.  Cerebellar atrophy primarily involving the vermis is common.  Behavioral problems, psychiatric symptoms, and even signs of dementia have been reported.  The vast majority of patients have cognitive disabilities and many become severely handicapped and immobile.  Early onset disease in children often leads to death within a few years whereas adults with later onset may live for many years.       

Females with leukoencephalopathy who live to puberty may experience ovarian failure, a condition sometimes called ovarioleukodystrophy.


This is an autosomal recessive disorder secondary to homozygous mutations in one of a group of five genes (EIF2B) located on chromosomes 1,2,3,12, and 14 encoding subunits of translation initiation factor 2B.    

Treatment Options: 

There is no effective treatment for the neurologic disease.  Ocular treatment for cataracts has not been reported.

Article Title: 


Alsalem A, Shaheen R, Alkuraya FS. Vanishing white matter disease caused by EIF2B2 mutation with the presentation of an adrenoleukodystrophy phenotype. Gene. 2012 Apr 1;496(2) :141-3.

PubMedID: 22285377

Labauge P, Horzinski L, Ayrignac X, Blanc P, Vukusic S, Rodriguez D, Mauguiere F, Peter L, Goizet C, Bouhour F, Denier C, Confavreux C, Obadia M, Blanc F, de S?(r)ze J, Fogli A, Boespflug-Tanguy O. Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases. Brain. 2009 Aug;132(Pt 8):2161-9.

PubMedID: 19625339