====== 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
==== Common Features ====
  * 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
==== Eye Features ====
  * Optic Atrophy
  * [[cherry_red_spot|Cherry-red Spot]] in macula
==== Diagnosis ====
  * 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 
==== Treatment ====
  * Bone Marrow Transplant
  * Clinical Trials
    * Gene Therapy
      * with autologous stem cell transplant 
      * intracerebral vector delivered genes
    * Intrathecal enzyme replacement therapy 
==== Reference ====
  * [[https://www.ncbi.nlm.nih.gov/books/NBK1130/|GeneReviews]]
  * [[https://www.ninds.nih.gov/Disorders/All-Disorders/Metachromatic-Leukodystrophy-Information-Page|National Institute of Neurological Disorders and Stroke]]

{{tag>syndrome}}