What is MLD?
Metachromatic leukodystrophy (MLD) is a recessive, genetic disorder. About 1 in 100 people carry a genetic mutation that can cause MLD but who will never suffer from the disease.
When two carriers of this mutation have a child, they have a 25% chance of passing both genetic mutations. That child will present with MLD. Those parents also have a 1 in 2 chance of having a child who is an unaffected carrier. These are only the general odds. Some families have three children, all of whom have MLD, and others can have four children, none with the disease. Younger siblings of diagnosed patients should be tested immediately to determine if they have MLD.
In late-infantile MLD, initial symptoms parents may notice are difficulty walking, impaired speech, and muscle weakness. With juvenile or adult onset MLD, first symptoms that can lead to a diagnosis include new problems with speech, behavioral and psychiatric problems, loss of muscle tone, and difficulty with balance, coordination, and walking.
There are general categories of this condition, loosely divided by when the disease presents:
Late infantile MLD — the most common. Parents typically notice symptoms around when the child begins to walk and gross motor skills are affected. Commonly misdiagnosed, most doctors do not correctly identify the disease as MLD until symptoms are more advanced, normally between two and three.
Juvenile MLD — less common than late infantile. Normally characterize MLD as juvenile if it presents past the age of three or four and before the teens. Presentation and progression can vary widely, depending on the mutation and at what age the disease presents. Often misdiagnosed as ADHD or other behavioral problems until fine or gross motor skills are affected.
Adult MLD — the least common form of MLD, occuring in about 10% of patients. Typically, this form of the disease progresses more slowly. Most present with an initial misdiagnosis of psychiatric disorders. Although cognitive decline is usually first to be noticed, some adults do have physical decline in the early stages of MLD.
Patients with MLD have two genetic mutations in the arylsulfatase A (ARSA) gene that together cause their body to not produce enough of an enzyme called arylsulfatase. Because there is little or low levels of this enzyme, the body cannot break down sulfatides and associated compounds, which are toxic to the brain and nervous system’s white matter or myelin. Since myelin protects the body’s nerves, this leads to nerve damage throughout the body and in the brain. At what age the body loses the ability to breakdown sulfatides depends on the combination of the two genetic mutations. With over 200 known variations of the mutated gene and few patients of each type, it can be difficult to project the disease some mutations will cause. It is for this reason, patient registries and corresponding natural history studies are critical so we can understand disease progression for every patient at the time of diagnosis.
How rare is MLD?
The truth is no one knows for sure. The incidence of MLD may range from 1 in 40,000 to 1 in 100,000, which means around 3,600 babies are born with the disorder each year. About 1 in 100 people are carriers of the ARSA mutation MLD. Two MLD carrier parents can have healthy children but there is also 25 percent chance they will have a child impacted by MLD.
Among the Navajo, the incidence of MLD is higher than the general population, approximately 1 in 2500.
Among certain Middle Eastern populations, MLD is believed to be even more common.
How is MLD diagnosed?
MRIs, blood and urine testing are common tools for diagnosing MLD. If you need MLD testing for yourself or a family member, you should contact the Lysosomal Storage Diseases Testing Lab at Thomas Jefferson University
Dr. Wenger has diagnosed more MLD patients than any other doctor in the world. Dr. Wenger is a world renowned expert in MLD and similar disorders. You can contact Dr. Wenger via email at David.Wenger@jefferson.edu.
Watch this video to learn more about Dr. Wenger’s work to diagnose and treat lysosomal storage diseases and leukodystrophies like MLD.