Metachromatic Leukodystrophy (MLD)

What is metachromatic leukodystrophy?

Metachromatic leukodystrophy (MLD) is a rare disease that falls under the larger category of leukodystrophy and is characterized by the destruction of the myelin sheath of nerve cells in the central and peripheral nervous systems. 

This disease presents in three forms, which are based on age of onset: late-infantile, juvenile, and adult. MLD as a whole is estimated to affect one of every 40,000 to 160,000 people, but those of Navajo descent and certain populations in the Middle East have a higher prevalence. 

What are the symptoms of metachromatic leukodystrophy?

Symptoms vary through the three subtypes of this disease, but all forms are progressive and share common symptoms. These common symptoms include intellectual and motor issues, difficulty talking, seizures, changes in behavior and personality, and difficulty walking. 

Late-infantile is the most common type, comprising about half of MLD cases. The peripheral nervous system is the first to be affected, leading to symptoms such as difficulty walking. 

The juvenile form is the second most common, accounting for 20-30% of cases, and onset can occur anywhere from four to fourteen. The first sign of this form is behavioral issues.

The adult form is the least common and has the latest onset. While it sees the latest onset, it shares the same final stage as the other types. This final stage sees symptoms such as blindness, unresponsiveness, and an inability to move or speak. 

What causes metachromatic leukodystrophy?

A mutated ASA gene is typically responsible for this disease, but a mutation in the PSAP gene is the cause in rare cases. Both of these genes are inherited in an autosomal recessive pattern. 

These genes result in an inability to break down fats, which contain sulfatides. The fats accumulate, resulting in the damage to the myelin sheath of neurons. 

How is metachromatic leukodystrophy diagnosed?

The diagnostic process typically begins when doctors notice the characteristic symptoms of MLD. They will then use tests such as MRIs, biochemical testing, and genetic testing. 

What are the treatments for metachromatic leukodystrophy?

The majority of treatment is symptomatic and supportive, but for children who have yet to present symptoms or have minimal symptoms, a stem cell transplant may be an option. 

Where can I find out more about metachromatic leukodystrophy?

• • NORD
  • NIH
  • Mayo Clinic