Revision 34 for 'Metachromatic leukodystrophy'

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Metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder. It is also classified as a dysmyelinating disease


With an estimated prevalence of ~1:100,000, it is considered the most common hereditary leukodystrophy. It typically manifests between 12 to 18 months of age. The condition carries an autosomal recessive inheritance.


Arises from a deficiency of an enzyme Arylsulphatase A as a result of mutation in the Arylsulphatase A (ARSA) gene located on chromosome 22q13. This results in accumulation of sulphides in various organs including the central nervous system impairing myelination.  

Metachromatic refers to the histologic staining characteristic caused by abnormal accumulations of sulfatides in white matter 6.

  • serum/urine arylsuphatase A levels: reduced

The disease can sometimes be according to the time of onset

  • late infantile: most common ~65% (range 50-80%)
  • juvenile (onset between 3-10 years)
  • adult (after age 16)
Clinical features
  • late infantile form: gait abnormality, muscle rigidity, loss of vision, impaired swallowing, convulsions, dementia
  • juvenile form: imparied school performance; similar features as in late infantile form but slower progression
  • adult form: psychiatric disorders and dementia; often protracted course over 10 years

Radiographic features

MRI Brain

Characterized by bilateral symmetrical confluent areas of periventricular deep white matter signal change, in particular around the frontal horns and atria with sparing of subcortical U fibers (see case 1). Progression can lead to cortical and sub cortical atrophy.

  • T1: affected areas are low signal
  • T1 C+ (Gd)
    • no enhancement is characteristic, however
    • some cases may show a linear punctate enhancement pattern within lesions 2
    • multiple cranial nerve enhancement has been reported 7
  • T2: affected areas are high signal and may show a "tigroid pattern": linear sparing along the venules
  • MR spectroscopy: (of affected white matter)
    • reduced N -acetylaspartate,
    • increased myo -inositol
    • increased lactate

Differential diagnosis

For a tigroid pattern of involvement, consider:

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