Metachromatic leukodystrophy (MLD) is a rare inherited disorder that causes progressive damage to the white matter (myelin) of the brain and nervous system. MLD is a severe, life-limiting condition. Prognosis depends on the age of onset, with earlier forms progressing more rapidly.

• Cause: Caused by mutations in the ARSA gene (most common) or PSAP gene, leading to a deficiency of the enzyme arylsulfatase A. This results in the buildup of toxic substances (sulfatides) that damage the myelin sheath. MLD is inherited in an autosomal recessive pattern.

• Features: Progressive loss of motor and cognitive abilities, muscle weakness, difficulty walking, seizures, vision and hearing loss, and eventually loss of the ability to speak or move. Symptoms vary by type:

  • Late-infantile (most common and severe): onset before age 4; Juvenile: onset between ages 4 and 16; Adult: onset after age 16, slower progression

• Diagnosis: Confirmed through enzyme testing, genetic testing, MRI (showing demyelination), and urine tests for sulfatides.

• Treatment: No cure. Supportive care is key. In select cases, stem cell transplant or gene therapy may slow progression if given early.