Does your child have these symptoms? Let's learn about ALD (Adrenoleukodystrophy)

Have you ever heard of a condition called ALD (Adrenoleukodystrophy)? The name may sound a bit complicated. But let's keep it simple. It's a genetic condition, meaning it's something we inherit from our parents. It specifically affects our nervous system and adrenal glands. Sometimes, these symptoms can be accompanied by behavioral changes and learning difficulties in young children.

What is ALD (Adrenoleukodystrophy)? Let's understand it simply.

Okay, let's first see what exactly ALD is. ALD is a rare disease that belongs to a group of genetic disorders . This group is called ``Leukodystrophies.'' Simply put, these diseases are caused by a change, or mutation, in our body's genes, that is, our ``DNA.'' Our ``DNA'' is like a set of instructions for how our body should function.

ALD is a progressive disease, meaning it gets worse gradually. Therefore, the primary goal of treatment is to slow the progression of the disease and provide patients with a better quality of life.

What happens to the body with ALD?

In a person with ALD, the body can't properly break down certain types of fat, especially Very-Long-Chain Fatty Acids (VLCFAs). This is like the garbage in our house that can't be removed. So, these VLCFAs start to accumulate in the brain, nervous system, and the adrenal cortex, which is the outermost part of the adrenal gland.

Scientists are still not entirely sure what exactly happens to the body when these VLCFAs accumulate. But research suggests that they cause inflammation and damage the protective covering around nerve cells in our brain, called the myelin sheath .

Think of it like the plastic sheath around a wire. When it's gone, the wire doesn't work properly. Similarly, when the myelin sheath is damaged, nerve cells can't send messages from the brain to the rest of the body. This can interfere with many bodily functions, such as walking and thinking.

ALD also damages the adrenal glands, which can lead to a decrease in certain hormones in the body. These adrenal glands are located above our kidneys. They produce hormones that affect male and female characteristics and hormones that respond to stress.

How is ALD inherited?

Because ALD is a genetic disease, it can be inherited from one or both parents. It is caused by a problem with the X chromosome , which is sometimes called X-linked ALD.

How common is ALD?

This is a very rare disease . Worldwide, it affects approximately one in 15,000 people. It is more common in men than in women.

What causes ALD?

The main cause of ALD is a mutation in a specific gene. Our genes are like a set of instructions for making proteins that are essential for the body to function. When a gene mutates, it can cause the wrong type of protein to be produced.

In ALD, the problem is in the gene called `(ABCD1)`. This gene produces a protein called `(ALDP)`. This protein is what helps break down the `(VLCFAs)` that we talked about earlier. So, because this protein is not produced properly, `(VLCFAs)` accumulate in the body's tissues.

What are the different types of ALD?

There are several main types of ALD:

• Childhood cerebral ALD: Boys with this type usually start showing symptoms of the nervous system between the ages of 3 and 10. Surprisingly, these children develop normally during infancy. Then, their abilities gradually start to decline. They often show behavioral problems, such as difficulty concentrating in school. Seizures may occur. The child may die within a few years of the onset of these symptoms.
• Addison's disease with ALD: Along with symptoms of the nervous system, ALD can cause the adrenal glands to stop working properly. This is called Addison's disease . In this condition, your adrenal glands don't produce enough of the hormone cortisol . Symptoms include loss of appetite and muscle weakness.
• Adrenomyeloneuropathy (AMN) or adult-onset ALD: This is a milder form of ALD. It usually begins between the ages of 21 and 35. People with AMN have problems with both the adrenal glands and the nervous system. Adult-onset ALD does not get worse as quickly as childhood ALD, but it can also cause brain function to decline in adults. Symptoms include leg cramps and pain in the limbs.

In addition to this, there are several other less common types of ALD:

• Adrenal insufficiency-only ALD: Some people can develop Addison's disease alone, without any problems with the nervous system. About one in ten people with ALD have this type.
• Adult cerebral ALD: About one in five adult men with the disease develop cognitive problems similar to those of childhood cerebral ALD. Over time, their mental and neurological function deteriorates significantly. Many adults with this type die from the disease.
• Females with ALD: About one in five women with ALD develop symptoms by the age of 40. By the age of 60, 90% have symptoms. However, symptoms are usually mild. For example, there may be mild weakness and stiffness in the legs.

When do ALD symptoms appear?

Symptoms of ALD usually begin between the ages of 3 and 10. However, they can sometimes begin later in life. The childhood-onset form of ALD is the most severe.

What are the common symptoms of ALD?

Each type of ALD has its own set of symptoms. Often, both neurological and hormonal symptoms are seen.

Symptoms of childhood cerebral ALD:

Symptoms seen in the early stages:

• Behavioral problems: For example, Attention Deficit Hyperactivity Disorder (ADHD) and learning disabilities.
• Cognitive deficits: These are difficulties in thinking and understanding new information. Children may feel "lost in a dream world" at school. They may have difficulty reading, writing, and solving spatial problems.
• Regression: This means that children lose their previous abilities.

As the disease progresses, you may also see symptoms such as:

• Vision problems
• Hearing impairment
• Difficulty walking
• Weakness and stiffness of limbs
• Convulsions and seizures
• Dementia
• Difficulty eating
• Vomiting

Eventually, children lose many of their nervous system functions. They lose sight, hearing, and voluntary movement. As the disease progresses, children enter a `vegetative state.' Children often die within two to three years of the onset of neurological symptoms.

Symptoms of Addison's disease:

Symptoms of decreased adrenal function:

• Fatigue
• Weight loss
• Nausea and vomiting
• Digestive problems
• Feeling weak
• Headaches in the morning
• Low blood pressure (Hypotension)
• Low blood sugar levels (Hypoglycemia)
• Darkening of the skin without exposure to sunlight (Hyperpigmented skin)

Adrenomyeloneuropathy (AMN) symptoms:

These include:

• Spasticity, weakness, or paralysis of the muscles in the lower limbs.
• Ataxia is a neurological condition that affects movement.
• Numbness and pain.
• Erectile dysfunction.
• Inability to control bowel movements (bowel incontinence).
• Difficulty controlling urine.
• Baldness due to premature aging.

Why does ALD affect men and women differently?

ALD is an X-linked genetic disease, meaning it is caused by a mutated gene on the X chromosome.

Females have two X chromosomes. They can be carriers of this disease. Usually, one X chromosome is "inactive." This means that the genes on that chromosome are not active.

Most of the time, women don't show symptoms because the mutated gene is on the "inactive" X chromosome. Women who do show symptoms usually develop a less severe form that appears in adulthood.

Males have only one X chromosome. Because there is no protection from an extra X chromosome, the mutated X chromosome can cause ALD to be more severe in males.

When is ALD diagnosed?

Some babies are diagnosed at birth during newborn screening . These tests check for certain diseases. In some countries, newborns are also tested for ALD during these screenings at the hospital. But most often, parents or doctors only suspect it when they notice symptoms in the child's first few years.

People with the adult-onset type are only diagnosed with the disease after seeing a doctor due to symptoms.

Who should get tested for ALD?

Parents and doctors should suspect ALD in these cases:

• If a boy with ADD or ADHD also has symptoms of a nervous system disorder.
• If a young man has problems walking or moving, and those problems are gradually getting worse.
• A man of any age can have Addison's disease, even if he has no other symptoms or problems.
• If an older woman gradually develops muscle weakness.

How is ALD diagnosed?

Doctors will review your child's medical history and family medical history. If ALD is suspected, your child may have tests such as:

• Blood test to measure the level of `(VLCFA)` in the blood.
• A genetic test to look for genetic changes associated with ALD or other conditions.
• Test the function of the adrenal glands with an adrenocorticotropic hormone stimulation test (ACTH stimulation test).
• An MRI scan is done to see how ALD has affected the brain.

If genetic testing confirms that you have ALD, your doctor may recommend that other family members also undergo genetic testing.

What are the treatments for ALD?

There is currently no cure for ALD. Treatment focuses on slowing the progression of the disease and controlling symptoms.

Treatment options depend on the type of ALD and symptoms. These may include:

• Adrenal hormone treatment: People with ALD need to have their adrenal glands checked regularly. Corticosteroid replacement therapy can treat adrenal insufficiency.
• Stem cell transplant: This is the only treatment that can slow the progression of ALD in children. If the disease is detected early, this transplant can stop the disease. If an MRI scan shows that ALD has affected the brain, but the child does not show clear symptoms on a neurological exam, doctors may recommend a stem cell transplant.
• Medications: Doctors may prescribe medications to help with symptoms such as tremors or muscle stiffness.

Other supportive treatments:

• Physical therapy.
• Psychological support.
• Special education.

Research-based treatments:

• Gene therapy: This can replace a defective gene with a normally functioning gene.
• Lorenzo's oil: This is a mixture of oleic acid and erucic acid. It is said to reduce the levels of VLCFA in the blood. If given to children before symptoms appear, it may delay or slow down the onset of symptoms.

What is the future of children with ALD?

The prognosis for a person with ALD depends on the type of disease. The prognosis for children with cerebral X-ALD is generally poor. Unless the disease is diagnosed early and stem cell transplantation is performed, their neurological function deteriorates. In most cases, children die within a few years of the onset of symptoms.

For people with adult-onset (AMN), the disease can progress slowly over decades.

Can ALD be prevented?

There is currently no known way to prevent ALD. If someone in your family has ALD, seek genetic testing and counseling as recommended by your doctor.

How should I treat my child with ALD?

Early intervention offers the best chance for successful treatment. If you notice any changes in your child's behavior or cognitive abilities, talk to your doctor right away. Also, if your child seems to be losing skills they once had, tell your doctor about this.

Your child's care team should include:

• Pediatrician.
• Pediatric and adult neurologist.
• Urologist.
• Endocrinologist.
• Psychiatrist.
• Physical therapist.
• Genetic counselor.
• Other specialists as needed.

What should I ask my doctor about ALD?

If your child is diagnosed with ALD, ask your doctor about the following:

• Can my child have a stem cell transplant?
• Does my child need steroid treatment?
• What will my child's future be like?
• What else can we do to reduce my child's symptoms?
• Should other family members undergo genetic testing?
• Are there any clinical trials my child can participate in?

Finally, things to remember

ALD is a genetic disease that affects the nervous system and adrenal glands. Symptoms often begin in childhood. If children lose their previous abilities or show changes in behavior, seek medical advice immediately. The sooner treatment for ALD is started, the more likely it is to slow the progression of the disease. There are several treatments for ALD, including stem cell transplants, medications, and supportive care. Your medical team will talk to you about your child's specific condition and future. Never panic, it is important to have the right information and follow your doctor's advice.

` ALD, Adrenoleukodystrophy, Genetic Diseases, Neurological Diseases, Pediatrics, Hormones, VLCFA