Metachromatic leukodystrophy

Last revised by Joshua Yap on 13 Jul 2022

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. 

Metachromatic leukodystrophy has an estimated prevalence of ~1:100,000 and typically manifests between 12 to 18 months of age. The disease can sometimes be classified 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 presentation depends on the age of onset. 

  • 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
    • adult presentation accounts for 20% of all cases
    • neuropsychiatric disorders
    • gradual cognitive decline and dementia
    • motor symptoms are a late feature
    • often protracted course over 10 years

Because sulfatide accumulates also in the wall of the gallbladder, cholecystitis is a recognized complication 8

Metachromatic leukodystrophy is classified as a dysmyelinating disease and carries an autosomal recessive inheritance. It arises from a deficiency of the enzyme arylsulfatase A as a result of a mutation in the arylsulfatase A (ARSA) gene located on chromosome 22q13. This results in the accumulation of 3-O-sulfogalactosylceramide (sulfatide) in various organs including the central nervous system (Schwann cells, oligodendrocytes, and some neurons) impairing myelination and function 8.  

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

  • serum/urine arylsulfatase A levels: reduced

Characterized 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 8. Occasionally, optic nerve enlargement can be seen 9.

  • 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
  • MR spectroscopy: (of affected white matter)
    • reduced N-acetyl aspartate (NAA)
    • increased myoinositol
    • increased lactate

Krabbe disease is one of the main differential diagnoses both clinically and by imaging 9. In addition to many of the other leukodystrophies, a tigroid pattern of involvement may also be seen in:

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Cases and figures

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