Answer of April 2009

Clinical History:

A 12 years-old-girl presented with ataxia and poor co-ordination since the age of 3. She was born full-term by spontaneously normal delivery. Her early developmental milestones were normal up to around 3 years old. There was progressive neurological deterioration after several admissions for febrile convulsion. Physical examination showed intentional tremors, muscle wasting and increased tone over bilateral upper and lower limbs. Her cognitive function was preserved.

She has consanguineous patients. Her paternal and maternal grandparents are sisters.

MRI brain was performed.

MRI:
T2W Axial

FLAIR Axial

Diagnosis:

Vanishing White Matter Disease

Discussion:

The T2-weighted image demonstrates a diffuse high signal of the periventricular white matter. The FLAIR image makes clear that large parts of the abnormal white matter have low signal intensity, similar to the signal intensity of cerebrospinal fluid, indicating white matter rarefaction and cystic degeneration.

Vanishing white matter disease was first described by Dr Van der Knaap (Free University Medical Center, Amsterdam, the Netherlands) in 1993.

It is characterized by a disease-free period followed by a chronic progressive and often episodic deterioration of motor skills in early childhood and yet relatively preserved cognition.

For the vanishing white matter disease, there are mutations in the EIF2B gene on chromosome 3q27. eIF2B plays a key role in the synthesis of protein under a variety of stress conditions, so-called ‘cellular stress response’. Defect in eIF2B explains the deterioration of vanishing white matter disease patients under conditions of stress e.g. infection. DNA analysis of this patient confirmed homozygous mutation in EIF2B with parents being heterozygous for the mutation.

MRI showed extensive T2 hyperintensity and, on Fluid Attenuated Inversion Recovery (FLAIR) imaging, areas that were of cerebrospinal fluid (CSF) signal intensity, in keeping with rarefaction and cystic degeneration of the periventricular white matter. The abnormal white matter in the vanishing white matter disease has a very characteristic MRI signal intensity signal that is consistent with CSF. This is in contrast to other leukoencephalopathies where the abnormal white matter may have signal intensity similar to CSF on T2 sequences but on FLAIR images differs.

Specific pharmalogical treatment for the condition is not available. The usual social, educational and occupational supports for children with these forms of disability are important. Immunization is indicated due to risk of infection on an affected child. Avoidance of situations that are likely to expose the child to an unnecessary risk of infection is recommended.