Canavan disease

Canavan disease, also known as spongiform degeneration of white matter (not to be confused with Creutzfeldt-Jakob Disease), is a leukodystrophy clinically characterised by megalocephaly, severe mental deficits and blindness. 

Pathology

It is an autosomal recessive disorder due to deficiency of N-acetylaspartoacylase (key enzyme in myelin synthesis), with resultant accumulation of NAA in brain, plasma, CSF and urine. Although its effects are wide spread, it has a predilection for subcortical U fibers and Alzheimer type II astrocytes in the gray matter.

Clinical onset is in infancy with death before 5 years of age, and often before 18 months.

Radiographic features

CT

The edematous sponginess of the white matter causes a characteristically low radiographic attenuation on CT so that it stands out in relief from the relatively unaffected gray matter ⁶.

MRI

There is often a large brain (megalencephaly)

There is typically a diffuse bilateral involvement of subcortical U-fibers ^2,4:

• T1: low signal in white matter
• T2: high signal in white matter
• MR spectroscopy: markedly elevated NAA and NAA:creatine ratio
  • this can be remembered using the mnemonic CaNAAvan

There is no enhancement of affected regions on either CT or MR.

Treatment and prognosis

The condition is fatal with death resulting at 2-5 years and treatment is generally supportive.

History and etymology

It was first described in 1931 by Myrtelle Canavan, American neuropathologist (1879-1953).

Differential diagnosis

Consider other dysmyelinating diseases such as

• Alexander disease (no NAA peak)
• Pelizaeus-Merzbacher disease
• adrenoleukodystrophy
• metachromatic leukodystrophy