General Condition Information
- X-linked adrenoleukodystrophy, childhood onset
- X-linked adrenyleukodystrophy
What is X-linked adrenoleukodystrophy
X-linked adrenoleukodystrophy (X-ALD) is an inherited (genetic) condition that prevents the body from breaking down certain fats.
The X-linked adrenoleukodystrophy protein (ALDP) is a transporter protein that brings a type of fat called very long-chain fatty acids (VLCFA) into peroxisomes to be processed. Peroxisomes are small areas inside your cells that perform important functions, including breaking down this type of fat.
In X-ALD, the protein ALDP is not made correctly, so these fats cannot enter peroxisomes to be processed. These VLCFA build up over time and damage the nervous system (including the brain and spinal cord) and the adrenal glands, which produce important hormones.
Damage caused by the buildup of VLCFA in the adrenal glands can prevent the adrenals from producing necessary hormones. This can make it harder to recover from infections or other stress. This damage, called adrenal insufficiency, is not ordinarily seen in babies but may develop as they get older. Adrenal insufficiency can be found with a blood test.
The VLCFA can also build up in the brain. About 35 percent of boys with this buildup develop the brain, or cerebral, form of X-ALD, which is the most severe. This condition usually occurs in boys 4 to 10 years old but can be earlier or later in life. There is also an adult form of the condition that affects the spinal cord, called adrenomyeloneuropathy (AMN). AMN is generally seen in young adults.
Newborn Screening and Follow-Up
Newborn screening for X-ALD is done using a small amount of blood collected from your baby's heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures the level of very long chain fatty acids in your baby's blood. Babies with high levels of these substances might have X-ALD. In some cases, elevated VLCFA levels require a second test. This second test looks for changes in the gene that causes X-ALD (called ABCD1). Newborn screening cannot tell what type of X-ALD a baby will have.
If your baby’s blood spot screening result for X-ALD is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare. Babies with other conditions that have elevated very long chain fatty acids may also be detected through this screening. An example of another condition that may be detected is Zellweger Spectrum Disorder.
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs and symptoms of X-ALD typically do not appear until childhood (as early as 2 years old, but more commonly between 4 and 10 years old). While there are no treatments yet that prevent these signs, monitoring can help catch and treat changes right away.
Signs of the condition in the adrenal gland may include the following:
- Decreased appetite
- Darker skin color
- Low blood sugar (hypoglycemia)
- Getting sicker than would be expected with an infection
Signs of the condition in the nervous system may include the following:
- Difficulties in maintaining attention
- Aggressive behavior
- Muscle weakness
- Poor coordination and motor control
- Difficulty swallowing
- Vision problems
- Hearing loss
- No longer being able to do things they could do before (milestone regression)
The condition is caused by a change in the ABCD1 gene. This gene gives your body instructions for making the ALDP transporter that helps peroxisomes break down very long-chain fatty acids.
Without a working ABCD1 gene, the body cannot make the ALDP transporter correctly. Very long-chain fatty acids are stuck on the outside of peroxisomes and not processed. These fats build up in the body, leading to damage to the nerves and adrenal glands.
- X-ALD is inherited in an X-linked recessive pattern, which means babies inherit this condition on their X chromosome.
- Baby girls have two X chromosomes. Only girls with two nonworking ABCD1 genes (one on each chromosome) have X-ALD. This is a very rare situation.
- Baby boys only have one X chromosome. All boys with one nonworking ABCD1 gene (on their only X chromosome) have X-ALD. This condition is more common in boys.
- Girls with one working copy and one nonworking copy of the ABCD1 gene are called carriers.
- Carriers for X-ALD may also have symptoms of the condition, but not generally until adulthood.
- Carriers may pass down a nonworking copy of the gene to their children.
- Parents who already have a boy with X-ALD still have a 1 in 2 chance of another son being born with X-ALD. Parents who have a girl who is an X-ALD carrier still have a 1 in 2 chance of having another girl that is an X-ALD carrier.
- All forms of X-ALD may be seen in the same family (cerebral form of X-ALD, adrenal insufficiency, AMN). Right now, we cannot tell who could have what type.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Regular monitoring of the nervous system (using magnetic resonance imaging [MRI]) and of the adrenal gland (using special blood tests)
- Hormone replacement if the adrenal glands are not functioning well. This is usually a pill taken several times daily.
- Stem cell transplantation, if the cerebral (brain) form of the condition is present
- Medicines for certain symptoms (e.g., stiffness and seizures)
- Physical therapy
Children who receive early and ongoing treatment for X-ALD can have better health outcomes than those who do not. Early stem cell transplantation can help prevent problems in children with nervous system symptoms. Treatment works best if it is given when changes are just beginning in the brain, before it becomes extensive and nervous system signs or symptoms start.