Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies. These diseases impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers. Myelin, which lends its color to the white matter of the brain, is a complex substance made up of at least 10 different enzymes.

The leukodystrophies are caused by genetic defects in how myelin produces or metabolizes these enzymes. Each of the leukodystrophies is the result of a defect in the gene that controls one (and only one) of the enzymes.

MLD is caused by a deficiency of the enzyme arylsulfatase A. MLD is one of several lipid storage diseases, which result in the toxic buildup of fatty materials (lipids) in cells in the nervous system, liver, and kidneys.

MLD has an autosomal recessive inheritance pattern.

There are three forms of MLD: late infantile, juvenile, and adult. In the late infantile form, which is the most common MLD, affected children have difficulty walking after the first year of life. Symptoms include:

  • Muscle wasting and weakness
  • Muscle rigidity
  • Developmental delays
  • Progressive loss of vision leading to blindness
  • Convulsions
  • Impaired swallowing
  • Paralysis
  • Dementia

Children may become comatose. Most children with this form of MLD die by age 5.

Children with the juvenile form of MLD (between 3-10 years of age) usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the infantile form but with slower progression.

The adult form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Adult-onset MLD progresses more slowly than the infantile form.

The prognosis for MLD is poor. It is a terminal illness. Most children with the infantile form die by age 5. The progression of symptoms in the juvenile and adult forms is slower and those affected may live a decade or more following diagnosis.

There is no cure for MLD. Bone marrow transplantation may delay progression of the disease in some cases. Other treatment is symptomatic and supportive.