Metachromatic Leukodystrophy (MLD)
Description
Metachromatic leukodystrophy (MLD) is a rare, inherited disorder that affects the nervous system. It is caused by a deficiency of the enzyme arylsulfatase A (ARSA), which is responsible for breaking down a fatty substance called sulfatides. Without this enzyme, sulfatides build up in the brain, spinal cord, and peripheral nerves, leading to damage and neurological decline.
Genes Involved
MLD is caused by mutations in the ARSA gene, located on chromosome 22. This gene provides instructions for making the ARSA enzyme.
Recognizing the Signs and Symptoms
The signs and symptoms of MLD vary depending on the age of onset. Early-onset MLD typically appears in infancy, while late-onset MLD can occur in childhood, adolescence, or adulthood. Common symptoms include:
- Developmental delays: In infants, this may involve delays in reaching milestones such as sitting, crawling, or walking.
- Seizures: Seizures can occur at any age and can vary in frequency and severity.
- Muscle weakness and stiffness: This can lead to difficulties with movement and coordination.
- Vision problems: This can include loss of peripheral vision, double vision, and nystagmus (involuntary eye movements).
- Hearing loss: This can occur at any age and may be progressive.
- Behavioral changes: This may include irritability, aggression, and difficulty concentrating.
- Dementia: This can occur in late-onset MLD and involves cognitive decline.
Causes
MLD is an inherited disorder, meaning it is passed down from parents to their children. In most cases, both parents carry a mutated copy of the ARSA gene, but do not have the disease themselves. There is a 25% chance that each child will inherit two mutated copies of the gene and develop MLD.
Inheritance/recurrence risk
MLD is inherited in an autosomal recessive pattern. This means that a person must inherit two copies of the mutated gene, one from each parent, to develop the disorder. If both parents carry the mutated gene, there is a 25% chance with each pregnancy that their child will inherit two copies of the mutated gene and develop MLD. There is a 50% chance that a child will inherit one copy of the mutated gene and be a carrier. There is also a 25% chance that a child will inherit two copies of the normal gene and not be affected by MLD.
