Metachromatic Leukodystrophy

Hereditary neurodegenerative disease caused by a deficiency of arylsulfatase A (ARSA) causing accumulation of sulfatides (a sphingolipid) in white matter
- Ccerebroside sulfate is a major lipid component of myelin and in high concentrations causes demyelination
- sulfatides are metachromatic sediments in the urine
One of the lysosomal storage diseases
Marked by progressive motor and neurocognitive dysfunction
Autosomal Recessive
Subtypes based on age of onset
- Late Infantile - onset in first 3 years of life (>50%)
- Juvenile - onset age 4- sexual maturity (20-30%)
- Adult- > age 16

Motor dysfunction
- difficulty walking
- Muscle wasting, weakness and rigidity
- Impaired swallowing
- Paralysis
Seizures
Progressive dementia
- May be preceded by personality changes or mild cognitive dysfunction

Serum ARSA enzyme level confirmed by elevated urine sulfatide
MRI Brain
- diffuse high signal on T2 or Proton Density
- diffuse symmetrical anterior leukoencephalopathy sparing the subcortical arcuate U fibers
Gene sequencing of ARSA gene
- over 200 mutations known and many mutations may not be pathologic
Nerve/brain biopsy

Bone Marrow Transplant
Clinical Trials
- Gene Therapy
  - with autologous stem cell transplant
  - intracerebral vector delivered genes
- Intrathecal enzyme replacement therapy