Metachromatic Leukodystrophy: Cases, Symptoms, Diagnosis and Treatment

Metachromatic leukodystrophy is a rare hereditary (genetic) disorder that results in an accumulation of lipids, or fats, in cells, particularly in the brain, spinal cord, and peripheral nerves. This buildup is caused by a deficiency of an enzyme known as sulfatide hydrolyzing enzyme. The damage to myelin, the substance that covers and protects nerve cells, causes the brain and nervous system to progressively lose their functional capacity.

There are three types of metachromatic leukodystrophy, each affecting a distinct age range: late infantile, juvenile, and adult. Signs and symptoms are subject to change. The infantile form is the most common and progresses more swiftly than the other forms.

The current treatment for metachromatic leukodystrophy is unknown. Depending on the type and age at which the condition first appears, early discovery and therapy may help manage some signs and symptoms and delay the disorder's progression.

Causes Of Metachromatic Leukodystrophy

Metachromatic leukodystrophy is a hereditary disorder caused by a mutant or abnormal gene. The disease is inherited in an autosomal recessive manner. Located on a non-sex chromosome called an autosome is the aberrant recessive gene.

 An autosomal recessive condition can only be inherited if both parents are carriers; however, carriers typically do not show symptoms. The affected child receives two copies of the faulty gene, one from each parent.

The most common cause of metachromatic leukodystrophy is mutations in the ARSA gene. This mutation results in the absence of the enzyme that breaks down the lipids called sulfatides that build up in the myelin.

Lack of activator protein, a distinct class of protein that breaks down sulfatides, is an infrequent cause of metachromatic leukodystrophy. The deadly buildup of sulfatides kills the white matter or cells that produce myelin, which protects the nerves. This results in functional impairment of the brain, spinal cord, and peripheral nerves.

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Symptoms Of Metachromatic Leukodystrophy

The following are some indicators that the myelin sheath enclosing the nerves is damaged: 

• Reduction in mental, cognitive, and memory capacities
• Loss of mobility and speech, as well as the inability to swallow and walk
• Tight, stiff muscles 
• Paralysis
• Reduction of bowel and bladder capacity
• Problems with the gallbladder
• Blindness
• Loss of hearing
• Seizures
• Behavioural and emotional issues, such as erratic moods and substance misuse;

 Each kind of metachromatic leukodystrophy has a unique age of start, spectrum of initial symptoms, and progression rate. Among these are:

• Late infancy: Usually affecting children under two, this is the most common kind of metachromatic leukodystrophy. Rapid deterioration of speech and motor function occurs gradually. Often, children of this kind do not survive to adulthood.
• Juvenile: Usually affecting children between the ages of three and sixteen, this is the second most common type. Behavioural and cognitive problems, together with increasing academic difficulties, are early warning signs. Walking is one of the abilities that might be lost. Though it advances more slowly than the late infantile form, the juvenile variant typically passes away 20 years after symptoms first appear.
• The adult's form: This variation is less prevalent and typically manifests itself after sixteen years of age. Drug and alcohol addiction, behavioural and mental health illnesses, and challenges at work or in the classroom are examples of signs that take time to manifest. Psychotic symptoms, such as delusions and hallucinations, could exist. This variant progresses distinctly, alternating between periods of stable symptoms and periods of severe functional losses. Adults may survive for several decades once their symptoms appear.

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Diagnosis Of Metachromatic Leukodystrophy

Your doctor will perform a physical examination, which may include a neurological exam, as well as review your medical history and symptoms to search for signs of metachromatic leukodystrophy.

To diagnose the condition, your physician may recommend various tests. These tests also help determine how serious the ailment is.

• Lab experiments: Blood samples are tested for the presence of an enzyme deficiency that causes metachromatic leukodystrophy. Urine tests can be used to determine a person's sulfatide levels.
• Genetic analyses: Your doctor might use genetic testing to look for changes in the gene linked to metachromatic leukodystrophy. He or she can also suggest prenatal testing, which involves looking for DNA changes in family members, particularly in expectant mothers.
• Nerve conduction study: This test uses skin electrodes to apply a tiny quantity of electricity to detect electrical nerve impulses as well as the function of muscles and nerves. This test may be used by your doctor to check for peripheral neuropathy, a condition that affects nerves and is frequently seen in patients with metachromatic leukodystrophy.
• MRI stands for magnetic resonance imaging: This technique creates remarkably detailed images of the brain by using radio waves and strong magnets. These may be able to detect a tigroid, also known as leukodystrophy, a striped pattern in the brain that is indicative of damaged white matter.
• Assessments of psychology and cognition: In addition to examining your behavior, your doctor may also assess your mental and cognitive functioning. These tests could be useful in figuring out how the illness impacts brain activity. Adolescent and adult metachromatic leukodystrophy types may initially present with behavioral and mental health issues as their primary symptoms.

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Treatment Of Metachromatic Leukodystrophy

Metachromatic leukodystrophy presently has no known cure, however clinical trials could eventually result in a workable treatment solution. The present treatment aims to protect nerves, avoid complications, shorten the duration of the condition, and provide supportive care. Early diagnosis and therapy may improve outcomes for certain affected persons.

As the illness progresses, more care is required to meet daily needs. Your healthcare team and you will work together to manage your symptoms and improve your overall quality of life. Talk about the possibility of participating in a clinical study with your doctor.

Treatments for metachromatic leukodystrophy include the following:

• Medicines: Among other indications and symptoms, drugs can reduce behavioural disorders, seizures, pain, gastrointestinal issues, sleeplessness, infections, and other conditions.
• Speech, physical, and occupational therapy: Physical therapy may be helpful to preserve range of motion and improve flexibility in the muscles and joints. Occupational therapy and speech therapy can help people continue to function.
• Dietary assistance: Working with a nutrition expert, or dietitian, can help you obtain appropriate nutrition. Eventually, it could become difficult to swallow food or drinks. As the disease progresses, assistance feeding equipment may be required.
• Substitute medical treatments: Further therapy may be needed if the sickness gets worse. Using a wheelchair, walker, or other assistive technology; needing hospitalisation or long-term care; requiring artificial ventilation to aid in breathing; and undergoing treatments to prevent or manage consequences are a few examples.

Treatment for metachromatic leukodystrophy can be difficult and change over time. Regular follow-up appointments with a team of medical professionals experienced in managing your condition may help prevent some repercussions and put you in touch with the appropriate people at home, at work, or in school.

Potential strategies for upcoming treatments

The following are some potential treatments for metachromatic leukodystrophy that are being researched:

• Gene therapy and other cell therapies involve replacing faulty genes with functional ones.
• Treatment with enhanced or substitute enzymes to lessen the buildup of fatty materials
• Treatment with substrate reduction, which lowers the output of fatty substances

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