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Disease Profile

X-linked adrenoleukodystrophy

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

X-ALD; Adrenoleukodystrophy; ALD


Metabolic disorders


X-linked adrenoleukodystrophy (X-ALD) is a genetic disease that affects the nervous system and the adrenal glands (small glands located on top of each kidney). People with this disease often have progressive loss of the fatty covering (myelin) that surrounds the nerves in the brain and spinal cord. They may also have a shortage of certain hormones that is caused by damage to the outer layer of the adrenal glands (adrenal cortex). This is called adrenocortical insufficiency, or Addison disease.[1] There are three forms of X-ALD: a childhood cerebral form, an adrenomyeloneuropathy (AMN) type, and an adrenal-insufficiency-only-type. The disease primarily affects males.[1]

X-ALD is caused by a variation (mutation) in the ABCD1 gene and it is inherited in an X-linked. manner. Diagnosis of the disease is based on testing the levels of a molecule called very long-chain fatty acids (VLCFA). The diagnosis can be confirmed with genetic testing. There is still no cure for X-ALD, but taking special oils such as Lorenzo’s oil can lower the blood levels of VLCFA. Bone marrow transplantation may be an option for boys who have evidence of brain involvement on MRI, but do not yet have obvious symptoms of the disease with a normal neurological exam. Adrenocortical insufficiency is treated with corticosteroids.[2]


X-linked adrenoleukodystrophy (X-ALD) symptoms are very varied. Basically there are three main types that are present in about 90% or 95% of the affected people: a childhood cerebral form or symptoms set 1, an adrenomyeloneuropathy (AMN) type or symptoms set 2, and an adrenal insufficiency-only type, or symptoms set 3. There are other other less common presentations (types) of the disease, known as symptoms sets 4 to 8:

  • Childhood cerebral form of X-ALD (or symptoms set 1): It mostly present with neurological problems, and typically begin between ages 4-8 years-old. The first noticeable symptom is usually behavior problems in school such as struggling to pay attention. Some boys may have seizures as their first symptom. As the disease progresses, other symptoms may include vomiting, vision loss, learning disabilities, trouble eating (dysphagia), deafnessfatigue, and trouble coordinating movements (ataxia).[2][3]
  • Adrenomyeloneuropathy (AMN) type (or symptoms set 2): Presents with both adrenal and neurological problems. It usually begin in early to mid-adulthood, and it is the most common presentation. Symptoms can include leg stiffness, weakness and pain in the hands and feet (peripheral neuropathy), muscle spasms and weakness, and urinary problems or sexual dysfunction.[2]
  • Adrenal insufficiency-only (Addison disease-only) type (or symptoms set 3): It is characterized by adrenal insufficiency without neurologic problems. Symptoms of adrenal insufficiency can develop at any time between childhood and adulthood and include decreased appetite, increased pigment (melanin) in the skin making it appear darker, muscle weakness, and vomiting.[4]

Symptoms seen in about 5%-10% of affected males may include:[2]

  • Symptom set 4: Onset is between age four and ten years but may occur in adolescence or, rarely, in adults, and may include headache, increased intracranial pressure, paralysis of one side of the body (hemiparesis) or visual field defect, difficulty speaking or other signs of localized brain disease.
  • Symptom set 5: Progressive behavioral disturbance, dementia, and paralysis in an adult
  • Symptom set 6: Progressive lack of coordination in a child or adult
  • Symptom set 7: Problems with urination and bowel abnormalities and occasionally impotence in at-risk males who have other affected relatives
  • Symptom set 8. No evidence of neurologic or endocrine dysfunction

Approximately 20% of female who are carriers develop mild to moderate weakness and spasticity (stiffness) of the legs (spastic paraparesis) in middle age or later. Adrenal function is usually normal.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

Dementia, progressive
Progressive dementia

[ more ]

Functional motor deficit
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Leg muscle stiffness
Progressive hearing impairment
Progressive spastic paraparesis
Sensory impairment
Specific learning disability
Visual loss
Loss of vision
Vision loss

[ more ]

30%-79% of people have these symptoms
Adrenal insufficiency
Aggressive behavior
Aggressive behaviour

[ more ]

Difficulty finding words
Losing words
Loss of words

[ more ]

Weakness of one side of body
Inappropriate sexual behavior
Increased circulating ACTH level
High blood corticotropin levels
Increased intracranial pressure
Rise in pressure inside skull
Neurogenic bladder
Lack of bladder control due to nervous system injury
Urinary bladder sphincter dysfunction
Visual field defect
Partial loss of field of vision
5%-29% of people have these symptoms
Double vision
Difficulty getting a full erection
Difficulty getting an erection

[ more ]

Inability to move
Percent of people who have these symptoms is not available through HPO
Abnormality of the cerebral white matter
Hair loss
Bowel incontinence
Loss of bowel control
Bulbar palsy
Elevated circulating long chain fatty acid concentration
Hearing impairment
Hearing defect

[ more ]

Hyperpigmentation of the skin
Patchy darkened skin
Decreased activity of gonads
Impaired vibration sensation at ankles
Decreased vibration sense at ankles
Decreased vibration sense in feet

[ more ]

Difficulties in coordination
Incoordination of limb movements
Limb incoordination

[ more ]

Limb ataxia
Loss of speech
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

Ongoing loss of nerve cells
Partial paralysis of legs
Peripheral nerve disease
Primary adrenal insufficiency
Worsens with time
Slurred speech
Spastic paraplegia
Truncal ataxia
Instability or lack of coordination of central trunk muscles
Urinary incontinence
Loss of bladder control


X-linked adrenoleukodystrophy (X-ALD) is caused by a variation (mutation) in the ABCD1 gene. This  gene provides instructions to make a protein called the adrenoleukodystrophy protein (ALDP). ALDP normally moves a type of fat molecule called very long-chain fatty acids (VLCFA) into a special part of the cell to be broken down. When the ABCD1 gene is changed, there is too little ALDP in the cells or the ALDP that is made does not work normally. This causes VLCFA to build up in the body. High levels of VLCFA are thought to be damaging to the outside of the adrenal glands (adrenal cortex) and the fatty covering (myelin) that surrounds the nerve cells in the brain and spinal cord. Researchers believe the damage caused by VLCFA may involve inflammation, especially in the brain.[1][2]


X-linked adrenoleukodystrophy (X-ALD) is suspected when a doctor observes signs and symptoms of the disease. X-ALD should be considered as a possible cause of symptoms in four situations:[2]

  • Boys with attention deficit disorder (ADD) who also have signs of neurological problems
  • Young men with progressive trouble walking or coordinating movements
  • All males with adrenal insufficiency (Addison disease), even in the absence of other symptoms
  • Adult women with progressive muscle weakness or wasting

If a diagnosis of X-ALD is suspected, a blood test of very long-chain fatty acids will detect elevated levels in 99% of males. Genetic testing can be used to confirm the diagnosis. After diagnosis, a brain MRI can be completed to determine the extent of the disease. A brain MRI will be abnormal even if symptoms of the disease are not very severe.[2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    The treatment for X-linked adrenoleukodystrophy (X-ALD) depends on the signs and symptoms present in each person and may include:[2][5]

    • Corticosteroids in case of adrenal insufficiency, which are used to normalize hormone levels.
    • Physical therapy that may be helpful for men with the adrenomyeloneuropathy (AMN) form of the disease. 
    • Bone marrow transplant, which is only recommended for boys who have brain involvement showed by brain MRI, but who have only minimal neurological or psychological findings, and who have normal clinical neurologic examination. This treatment have many risks and it is not recommended in cases of severe neurologic symptom.
    • Lorenzo’s oil, recommended for boys who do not yet have symptoms of X-ALD.[5] However, this treatment is experimental, and the treatment's exact benefit has not been definitively shown, but it may slow down the progression of the disease.

    Clinical trials investigating treatment with gene therapy are currently underway and have shown some preliminary success.[2][6]


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on X-linked adrenoleukodystrophy . This website is maintained by the National Library of Medicine.
        • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked adrenoleukodystrophy . Click on the link to view a sample search on this topic.


            1. X-linked adrenoleukodystrophy. Genetics Home Reference (GHR). July 2013; https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy.
            2. Steinberg SJ, Moser AB, and Raymond GV. X-linked Adrenoleukodystrophy. GeneReviews. April 9, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1315/.
            3. Adrenoleukodystrophy (ALD). Kennedy Krieger Institute. https://www.kennedykrieger.org/patient-care/diagnoses-disorders/adrenoleukodystrophy-ald.
            4. Haldeman-Englert C. Adrenoleukodystrophy. MedlinePlus. October 27, 2015; https://www.nlm.nih.gov/medlineplus/ency/article/001182.htm.
            5. Adrenoleukodystrophy Information Page. National Disorders of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Adrenoleukodystrophy-Information-Page. Accessed 11/1/2017.
            6. Eichler F, Duncan C, Musolino PL, Orchard PJ, de Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB, Gissen P, Amartino H, Bratkovic D, Smith NJC, Parker AM, Shamir E, O’Meara T, Davidson D, Aubourg P, and Williams DA. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. The New England Journal of Medicine. 2017; 377:1630-1638. https://www.nejm.org/doi/10.1056/NEJMoa1700554#t=articleTop.

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