Metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) is the most common hereditary (autosomal recessive) leukodystrophy and is one of the lysosomal storage disorders. It has characteristic imaging features including peri-atrial and to a lesser extent frontal horns leukodystrophy as well as periventricular perivenular sparing results in "tigroid pattern" on fluid sensitive MRI sequences. 

It has an estimated prevalence of ~1:100,000 and typically manifests between 12 to 18 months of age. 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)
  • late infantile form: gait abnormality, muscle rigidity, loss of vision, impaired swallowing, convulsions, dementia
  • juvenile form: impaired school performance; similar features as in late infantile form but slower progression
  • adult form: psychiatric disorders and dementia; often protracted course over 10 years

Metachromatic leukodystrophy is classified as a dysmyelinating disease, and carries an autosomal recessive inheritance. It arises from a deficiency of an enzyme arylsulfatase A as a result of mutation in the arylsulfatase A (ARSA) gene located on chromosome 22q13. This results in accumulation of sphingolipids 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.

Markers
  • serum/urine arylsulfatase A levels: reduced
MRI

Characterised by bilateral symmetrical confluent areas of periventricular deep white matter signal change, in particular around the atria and frontal horns with sparing of subcortical U fibers leading to a "butterfly pattern". Progression can lead to cortical and subcortical atrophy.

Signal characteristics
  • 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" on axial plane or "leopard pattern" on sagittal plane: sparing along the venules
  • MR spectroscopy: (of affected white matter)
    • reduced N-acetylaspartate
    • increased myo-inositol
    • increased lactate

For a tigroid pattern of involvement, consider:


Inborn errors of metabolism
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Article Information

rID: 10322
Section: Pathology
Synonyms or Alternate Spellings:
  • MLD
  • Metachromatic leucodystrophy
  • Arylsulphate A deficiency

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