X-linked adrenoleukodystrophy is a rare genetic condition that causes problems with the white matter in your nervous system and adrenal glands.

X-linked adrenoleukodystrophy (X-ALD) is a genetic condition passed through families on the X chromosome.

The name “Adrenoleukodystrophy” can be broken into three parts:

  • “Adreno” refers to your adrenal glands.
  • “Leuko” refers to white matter in your nervous system.
  • “Dystrophy” means tissue breakdown.

People with X-ALD develop degeneration of the white matter in their brain, spinal cord, and adrenal glands due to a mutation of the ABCD1 gene. This mutation leads to an inability to break down very long-chain fatty acids (VLCFAs).

The outlook for X-ALD varies widely. Some people develop severe symptoms in childhood, while others develop mild symptoms in adulthood.

Read on to learn more about X-ALD, including its symptoms, treatment options, and outlook.

How common is X-ALD?

X-ALD is estimated to affect between 1 in 10,000 to 1 in 17,000 people. It may be underreported since it may often go undiagnosed.

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An ABCD1 gene mutation on your X chromosome causes X-ALD. Females have two X chromosomes, while males have one X and one Y chromosome.

Because females have an extra copy, they develop X-ALD less often and usually develop milder disease later in life.

Associated ABCD1 mutations cause a type of fat called VLCFAs to accumulate in your nervous system and adrenal glands. This buildup of VLCFAs can result in a loss of the fatty layer covering the nerves in your brain and spinal cord called myelin.

Experts think that damage to myelin might occur due to an inflammatory response from your immune system.

The signs and symptoms of X-ALD can vary widely. The sections below look at the symptoms of each type of ALD, with statistics from the National Organization for Rare Disorders (NORD).

Childhood ALD

About 35% of males develop neurological symptoms between the ages of 3 and 10 years. Symptoms rarely develop before the ages of 2.5 to 3 years.

Signs and symptoms may include:

Many children also have Addison’s disease, which is characterized by the underproduction of cortisol and aldosterone by the adrenal glands.

Addison’s disease can cause:

Childhood ALD typically progresses to a vegetative state within 2 to 3 years from the onset of neurological symptoms.


Adrenomyeloneuropathy is a form of X-ALD that onsets from the late 20s to middle age. It affects almost all males with the ABCD1 gene mutation who don’t develop childhood disease.

It causes symptoms like:

  • progressive stiffness and weakness in your legs
  • walking problems
  • neuropathy, which causes numbness and pain in your limbs
  • erectile dysfunction
  • bladder and bowel control issues
  • premature balding

Adult cerebral ALD

At least 20% of people with the adult form of X-ALD develop cognitive decline similar to that seen in the childhood form. It usually results in severe neurological impairment and, eventually, a vegetative state.

Addison’s-only ALD

About 10% of people with X-ALD only have symptoms of Addison’s disease.

X-ALD in females

Females who carry an associated gene mutation often develop symptoms in adulthood. Symptoms are usually less severe. About 20% of female gene carriers under 40 years old develop symptoms, but this increases to 90% by age 60 years. Addison’s disease and brain involvement are rare in females.

Symptoms include:

  • unbalanced gait
  • neuropathy
  • weakness

X-ALD can cause mild to severe complications. People with the most severe forms of the disease can develop:

  • blindness
  • deafness
  • inability to move
  • seizures
  • coma

Death is also a possible result.

People with milder forms might develop complications like:

  • bladder or bowel incontinence
  • symptoms of Addison’s disease
  • erectile dysfunction
  • limb pain or numbness

It’s important to contact your child’s doctor if you believe they may have:

  • a learning difficulty
  • cognitive impairment
  • developmental problems
  • seizures

For adults, it’s a good idea to seek medical attention any time you develop neurological symptoms like:

  • unexplained headaches
  • tingling or numbness
  • bladder or bowel control issues

A doctor may suspect X-ALD if you or your child has characteristic signs and symptoms. Along with doing a review of your symptoms, your doctor may:

  • Review your personal and family medical history.
  • Perform a physical exam.
  • Order blood tests to look for associated gene mutations and measure levels of VLCFAs.
  • Perform an ACTH stimulation test to measure adrenal gland function.
  • Order MRI to monitor changes in brain structure.

Some infants may receive a diagnosis during newborn screening. It was added to the Uniform Newborn Screening Panel in the United States in 2016, but each state determines which disease it will test for. Almost all states now screen for X-ALD.

A doctor may consider an allogenic hematopoietic stem cell transplant (HSCT) for males with MRI findings that don’t yet show neurological symptoms. An allogeneic HSCT involves injecting stem cells from the bone marrow of a donor into your child’s bloodstream.

Some research suggests that HSCT may stop the progression of neurological symptoms, but it doesn’t improve adrenal insufficiency. It also comes with some potentially serious risks, like graft-versus-host disease.

The Food and Drug Administration (FDA) approved the gene therapy drug elivaldogene autotemcel (Skysona) in 2022 to slow the progression of neurological dysfunction in boys ages 4 to 17 years. Although it may slow disease progression, the FDA includes a boxed warning that it may increase the risk of blood cancer.

Addison’s disease is treatable with hormone replacement like oral corticosteroids to replace cortisol.

The outlook tends to be poor for people with X-ALD who develop symptoms early in childhood, and most children pass away before adolescence. Early treatment may effectively slow or halt the progression of the condition.

Can you live a normal life with X-linked adrenoleukodystrophy?

Some people who develop X-ALD in adulthood only have mild symptoms. They may never develop symptoms affecting their brain and may have minimal disability. Females tend to have milder symptoms than males.

The outlook for X-ALD varies widely. Many children who develop symptoms early in childhood pass away before adolescence, but some people may only ever develop mild symptoms in adulthood.

HSCT and gene therapy have emerged as potential treatment options for X-ALD. These treatments are most effective when initiated early in the progression of the condition.