A genetic disorder that causes a progressive decline in the mental and motor (movement) functions. The word “progressive” means the symptoms worsen over time. Doctors often recommend occupational therapy, a feeding tube, and medicines to treat this condition.
In other words, a rare genetic condition that negatively affects the white matter of the central nervous system (including the brain and spinal cord) and peripheral nerves is called metachromatic leukodystrophy (MLD). Moreover, this condition is a type of lysosomal storage disease.
However, damage to the white matter happens when certain fatty materials (called sulfatides) begin to build up in the cells. As a result, it impairs the growth of the myelin sheath (the protective layer of the nerve fiber). This protective layer gives the white matter its color. People with MLD often experience a decline in mental and motor functions.
The name of this condition comes from the way cells with a buildup of sulfatides appear when you look at them under a microscope. Hence, the sulfatides appear metachromatic, which means they have different colors than the surrounding cellular material. The medical term “leukodystrophy” means progressive destruction of the white matter.
This disorder occurs quite rarely and affects 1 in every 40,000 people in the U.S. MLD is more common in some isolated populations, such as the Navajo, who have a higher prevalence rate of 1 in every 2,500 people.
Types of Metachromatic Leukodystrophy
Doctors have divided this condition into 3 categories. For example:
- Late infantile MLD – This type of MLD often occurs in babies between 12 and 20 months of age. Usually, they experience walking problems, developmental delays, blindness (loss of vision), and dementia. Most of the time, babies with MLD die by age 5. Furthermore, this is the most common type of MLD, and it accounts for about 50% to 60% of all diagnosed cases.
- Juvenile MLD – This type negatively affects children between the ages of 3 and 10. Most children who develop this type of MLD experience intellectual decline, behavioral changes, seizures, and dementia. People with juvenile MLD often live between 10 and 20 years after diagnosis, and this form accounts for about 20% to 30% of diagnosed cases.
- Adult MLD – Most people with this condition have noticed the first symptoms at the age of 16. These include seizures, psychiatric changes, and dementia. Death often occurs within 6 to 14 years after the diagnosis is confirmed by the doctors. This type of MLD accounts for approximately 15% to 20% of all diagnosed cases.
Symptoms
The symptoms often appear differently among people who develop MLD. They often depend on the severity and type of MLD, existing health problems, gender, and age. Check below some symptoms according to the type of condition:
Late Infantile MLD Symptoms
Check below some symptoms that often appear in babies with late infantile MLD in the first year of life:
- Walking problems (sometimes, an inability to walk)
- Hypotonia (weak muscle tone)
- Developmental delays
- Dysarthria (speaking problems)
- Progressive vision loss, which leads to a complete loss of vision (also known as blindness)
- Dysphagia (swallowing problems)
- Dementia
Juvenile MLD Symptoms
These include:
- Behavioral changes
- Inability to control muscles
- Seizures
- Dementia
- Peripheral neuropathy
- Personality changes
- Intellectual decline
Adult MLD Symptoms
While the primary symptom of adult MLD is psychiatric changes with or without motor symptoms, it may also cause alcohol use disorder, substance use disorder, and/or difficulties at work or school. Check below for other symptoms of adult MLD:
- Peripheral neuropathy
- Seizures
- Dementia
- Hallucinations
- Psychosis
- Schizophrenia
Moreover, some physicians may misdiagnose adult MLD as bipolar disorder or dementia. In any case, if any of the symptoms listed above occur, immediately contact your healthcare professional. Otherwise, it may lead to serious and even life-threatening complications (such as death).
Causes
This condition happens due to a genetic mutation (change) that people often inherit from their biological parents during conception. Most of the time, people with MLD have a mutation in the ARSA gene, which is responsible for producing an enzyme called arylsulfatase A. Normally, this enzyme is involved in the process that breaks down sulfatides. However, in people with this genetic mutation, the body does not produce enough arylsulfatase A, which causes a buildup of sulfatides. In other words, excessive sulfatides are toxic to the white matter in the nervous system, which causes damage to these cells. In rare cases, people with MLD have a mutation in their PSAP gene, which also helps break down sulfatides.
Is Metachromatic Leukodystrophy Genetic?
Yes, the gene that causes this condition passes from biological parents to their children in an autosomal recessive pattern. In most cases, parents do not have signs of this condition because they are carriers and have only one abnormal gene. If your children get only one abnormal gene, they will also become carriers who may pass this abnormal gene to their children in the future.
What Are The Long-term Effects of Metachromatic Leukodystrophy?
Those who develop MLD may also experience some complications, especially if the condition is left untreated. Check some examples below:
- Motor and neurological decline – This complication causes progressive loss of ability to walk, sit, or move. In most cases, it starts with ataxia and severe muscle stiffness (spasticity).
- Cognitive and behavioral changes – These include severe cognitive decline, dementia, and hallucinations or delusions (sometimes).
- Sensory loss – People who develop MLD may also experience a complete loss of vision (blindness).
- Aspiration pneumonia
- Incontinence (including bowel and bladder)
- Malnutrition
- Joint and bone issues
- Gallbladder dysfunction
- Death
The previous list does not contain a full list of complications, but you can talk with your doctor about preventive measures. In addition, there is no way to prevent MLD because it occurs due to an abnormal gene that is passed from the biological parents during conception. However, you can perform some genetic tests before pregnancy to make sure you do not have the abnormal gene that causes MLD. It is very important to understand the risks of having children with metachromatic leukodystrophy.
Diagnosis
When doctors suspect MLD, they will refer your child to a neurologist for further testing. The diagnosis often begins with a neurological and physical examination to check for irregularities linked to the disease. Doctors may also perform the following tests to exclude other health conditions that cause similar symptoms. Check some examples below:
- Genetic test – During this test, doctors will take a sample of blood to check for mutations in the ARSA and PSAP genes.
- Biochemical testing – To perform this test, physicians will take samples of urine and blood to measure the levels of sulfatides.
- Brain MRI (magnetic resonance imaging) – This is an imaging test used to get detailed images of the brain and nearby structures. It often helps detect the presence or absence of myelin.
Furthermore, doctors may also perform additional tests once your child is diagnosed with MLD. These include neuropsychological testing, nerve conduction tests, and neurocognitive tests. They help identify the affected part of the nervous system and make the best treatment plan for your child.
Treatment
Unfortunately, it is not possible to cure this condition. That’s why the treatment goal is to ease the symptoms, prevent serious complications, and improve your child’s quality of life. Sometimes, stem cell transplants are enough to slow the progression of MLD in mild cases. Check below for other options used to treat MLD:
- Physical therapy to improve muscle strength and stiffness
- Occupational therapy to improve the ability to perform daily activities
- Speech therapy to help with speaking and swallowing problems
- Psychotherapy to help with negative thoughts and other mental health problems
- Percutaneous endoscopic gastronomy (PEF) – This treatment is often recommended by doctors for people with MLD to help with feeding problems.
Doctors may also recommend the following medications to help relieve the symptoms. For example, anti-seizure medicines, muscle relaxants, NSAIDs (nonsteroidal anti-inflammatory drugs) to ease pain, and antidepressants.
Frequently Asked Questions
What is the life expectancy of someone with metachromatic leukodystrophy?
This is a severe and progressive genetic disorder that negatively affects lifespan. However, it significantly varies by age of onset. For instance, with earlier onset, the condition worsens quickly and may cause paralysis and death by the age of 10, but the adult form of the condition is less severe, and people can live from 10 to 30 years after diagnosis. However, most adults with MLD often die from infections (such as pneumonia).
When should I see my healthcare provider?
If you suspect you or your child has MLD, or you experience symptoms similar to this genetic disorder, immediately contact your healthcare professional because the condition often worsens quickly. Early diagnosis and proper treatment may help ease the symptoms and reduce the mortality rate.
What are the symptoms of leukodystrophy in adults?
Usually, people who develop this condition experience the following symptoms. For example, ataxia (balance and movement issues), paralysis (loss of muscle function), and spasticity (abnormal muscle tightness). If you have any other questions, ask your healthcare provider.
