Metachromatic Leukodystrophy

What is Metachromatic Leukodystrophy?

Also known as MLD, metachromatic leukodystrophy is an inherited disorder that occurs when fats called sulfatides collect in the cells. This accumulation causes damage to the white matter in the brain, affecting motor skills and cognitive function.

There are three major forms of MLD: late-infantile, juvenile and adult onset MLD. Late-infantile MLD is the most common form of the disease. Less common types of MLD include saposin B deficiency and multiple sulfatase deficiency.

What causes MLD?

MLD is an inherited disorder that follows an autosomal recessive pattern. This means that two copies of a defective gene must be present in order for a child to develop the condition. If only one defective copy is passed down, this means that the child will be a carrier but will display no symptoms. If no copies are passed down, the child will not carry the gene and they will not have any symptoms.

In most cases, MLD relates to mutations that affect the ARSA gene. This gene contains instructions that are associated with the production and function of the enzyme arylsulphatase A (ASA). Arylsulphatase A is present in cells called lysosomes and its role is to break down sulfatides. If the enzyme doesn’t work properly, this contributes to an accumulation of sulfatides. When there are excessive levels of sulfatides in the cells, this becomes toxic and the function of the nervous system is affected. The build-up of sulfatides interferes with the cells that produce myelin, eventually destroying them.

Who is affected?

MLD is rare. It affects 1 in every 40,000-160,000 people.

What are the symptoms?

Symptoms may vary according to the type of MLD.

Late-infantile MLD

During early infancy, there may be no symptoms and growth and development may appear normal. Once symptoms develop, they tend to progress quickly and children may be bed-bound for prolonged periods of time. Symptoms include:

• speech problems and eventual loss of speech
• dysphagia (swallowing difficulties)
• disturbed vision and eventual loss of sight
• delayed development
• loss of muscle tone (hypotonia)
• seizures
• increased susceptibility to infections
• loss of coordination in muscle movements (ataxia)
• abnormal eye movements and being cross-eyed

Juvenile MLD

The symptoms of juvenile MLD tend to develop between the ages of 4 and 12 years old and are generally noticed when children start to struggle with school work or experience problems with mobility and movement. Symptoms include:

• clumsiness and unsteadiness
• slurred speech
• shakes and tremors
• incontinence

In the latter stages, the symptoms are similar to those associated with late-infantile MLD.

Adult MLD

Symptoms may develop at any age from 14 to 50 years old. Early signs include changes in behaviour and personality and impaired performance at work. After the initial onset of symptoms, symptoms tend to get worse over the next 10-30 years and motor and cognitive abilities are affected.

How is MLD diagnosed?

If there are symptoms of MLD and a diagnosis of MLD is suspected, tests will be ordered to confirm a diagnosis and rule out other possible causes. Tests that may be carried out include:

• tests to measure the activity of the ASA enzyme
• imaging scans (such as an MRI scan)
• genetic testing

Treatment for MLD

There is currently no cure for MLD and the only treatment options are a bone marrow transplant and stem cell transplant. These procedures can help to slow down the progress of the disorder in cases where symptoms are not yet severe. Research in this area is ongoing.