Adrenoleukodystrophy

Adrenoleukodystrophy

Overview

Adrenoleukodystrophy (uh-dree-noh-loo-koh-DIS-truh-fee) is a type of hereditary (genetic) condition that damages the membrane (myelin sheath) that insulates nerve cells in your brain.

In adrenoleukodystrophy (ALD), your body can't break down very long-chain fatty acids (VLCFAs), causing saturated VLCFAs to build up in your brain, nervous system and adrenal gland.

The most common type of ALD is X-linked ALD, which is caused by a genetic defect on the X chromosome. X-linked ALD affects males more severely than females, who carry the disease.

Forms of X-linked ALD include:

Childhood-onset ALD. This form of X-linked ALD usually occurs between ages 4 and 10. The white matter of the brain is progressively damaged (leukodystrophy), and symptoms worsen over time. If not diagnosed early, childhood-onset ALD may lead to death within five to 10 years.

Addison's disease. Hormone-producing glands (adrenal glands) often fail to produce enough steroids (adrenal insufficiency) in people who have ALD, causing a form of X-linked ALD known as Addison's disease.

Adrenomyeloneuropathy. This adult-onset form of X-linked ALD is a less severe and slowly progressive form that causes symptoms such as a stiff gait and bladder and bowel dysfunction. Women who are carriers for ALD may develop a mild form of adrenomyeloneuropathy.

Symptoms

ALD symptoms often appear between the ages of 3 and 10, though they can start later in life. The childhood form of ALD is the most severe.

Each type has its own symptoms. People often have both neurological and hormonal symptoms.

Childhood cerebral ALD symptoms:

Early symptoms include:

Behavioral problems, such as attention deficit hyperactivity disorder (ADHD) and learning disabilities.

Cognitive deficits, or problems with thinking and processing new information. Children may “space out” at school. They may have trouble with reading, handwriting and solving spatial problems.

Regression, when children lose skills.

As the disease progresses, symptoms include:

Vision problems.

Hearing loss

Trouble walking.

Weak and stiff limbs.

Convulsions and seizures.

Dementia.

Trouble eating.

Vomiting.

Eventually, children lose most of their neurological abilities. They lose sight, hearing and voluntary movements. As the disease progresses, children end up in a vegetative state. They often pass away within two to three years of the neurological symptoms’ starting.

Addison’s disease symptoms:

Symptoms of adrenal insufficiency include:

Fatigue.

Weight loss.

Nausea and vomiting.

Digestive problems.

Feeling weak.

Headaches in the morning.

Hypotension.

Hypoglycemia.

Hyperpigmented skin, when the skin darkens unrelated to sun exposure.

Adrenomyeloneuropathy symptoms:

Symptoms include:

Spasticity (muscle stiffness), weakness or paralysis of the lower limbs.

Ataxia, neurological conditions affecting movement.

Numbness and pain.

Erectile dysfunction.

Bowel incontinence.

Bladder control problems.

Premature baldness.

Causes

The cause of ALD is a mutation in a particular gene. Your genes are the instruction manual for creating proteins that have critical roles in how the body works. With a genetic mutation, the gene may create faulty protein.

With ALD, there’s a problem with the ABCD1 gene, which creates the ALDP protein. This protein helps break down VLCFAs. Because of the faulty protein, VLCFAs accumulate in the body’s tissues.

The most common forms of ALD are:

Childhood cerebral ALD: Boys with this form of ALD usually start showing neurological symptoms between ages 3 and 10. As infants, these children develop typically. Then they begin to regress, losing skills. Children often display behavioral problems, such as having difficulty paying attention in school. They may also have seizures. Children with this type typically pass away within a few years of developing symptoms.

ALD plus Addison’s disease: Along with neurological symptoms, ALD may cause adrenal insufficiency, or Addison’s disease. This condition means your adrenal glands don’t make enough of the hormone cortisol. Symptoms include decreased appetite and muscle weakness.

Adrenomyeloneuropathy (AMN) or adult-onset ALD: This milder form of ALD begins between ages 21 and 35. People with AMN have both adrenal and neurological problems. Adult-onset ALD progresses more slowly than childhood cerebral ALD, but adults can also have deteriorating brain function. Other symptoms include leg stiffness and pain in the hands and feet.

Less-common types of ALD include:

Adrenal insufficiency-only ALD: Some people have only Addison’s disease, without any neurological problems. About 1 in 10 people with ALD have this type.

Adult cerebral ALD: About 1 in 5 affected adult males develop cognitive problems similar to childhood cerebral ALD. Over time, they lose most of their mental and neurological function. Many adults with this type eventually pass away from the disease.

Females with ALD: By age 40, about 1 in 5 women who are ALD carriers have symptoms, but 90% have symptoms by age 60. Symptoms generally less severe, such as mild weakness and stiffness in their legs.

Diagnosis

To diagnose ALD, your doctor will review your symptoms and your medical and family history. Your doctor will conduct a physical examination and order several tests, including:

Blood testing. These tests check for high levels of very long-chain fatty acids (VLCFAs) in your blood, which are a key indicator of adrenoleukodystrophy.

Doctors use blood samples for genetic testing to identify defects or mutations that cause ALD. Doctors also use blood tests to evaluate how well your adrenal glands work.

MRI. Powerful magnets and radio waves create detailed images of your brain in an MRI scan. This allows doctors to detect abnormalities in your brain that could indicate adrenoleukodystrophy, including damage to the nerve tissue (white matter) of your brain. Doctors may use several types of MRI to view the most-detailed images of your brain and detect early signs of leukodystrophy.

Vision screening. Measuring visual responses can monitor disease progression in males who have no other symptoms.

Skin biopsy and fibroblast cell culture. A small sample of skin may be taken to check for increased levels of VLCFA in some cases.

Treatment

Adrenoleukodystrophy has no cure. However, stem cell transplantation may stop the progression of ALD if done when neurological symptoms first appear. Doctors will focus on relieving your symptoms and slowing disease progression.

Treatment options may include:

Stem cell transplant. This may be an option to slow or halt the progression of adrenoleukodystrophy in children if ALD is diagnosed and treated early. Stem cells may be taken from bone marrow through bone marrow transplant.

Adrenal insufficiency treatment. Many people who have ALD develop adrenal insufficiency and need to have regular adrenal gland testing. Adrenal insufficiency can be treated effectively with steroids (corticosteroid replacement therapy).

Medications. Your doctor may prescribe medications to help relieve symptoms, including stiffness and seizures.

Physical therapy. Physical therapy may help relieve muscle spasms and reduce muscle rigidity. Your doctor may recommend wheelchairs and other mobility devices if needed.

In a recent clinical trial, boys with early-stage cerebral ALD were treated with gene therapy as an alternative to stem cell transplantation. Early results from gene therapy are promising. Disease progression stabilized in 88 percent of boys who participated in the trial. Additional research is necessary to assess long-term results and safety of gene therapy for cerebral ALD.

Type of Doctor Department : A pediatrician, neurologist, endocrinologist, urologist, and/or geneticist