X-linked adrenoleukodystrophy

Información en español Title

Other Names:

X-ALD; Adrenoleukodystrophy; ALD

Categories:

Metabolic disorders

Subtypes:

Adrenomyeloneuropathy; Childhood-onset cerebral X-linked adrenoleukodystrophy; Peroxisomal beta-oxidation disorder

This disease is grouped under:

Disorder of peroxisomal alpha-, beta- and omega-oxidation; Disorders with deficiency of a single peroxisomal enzyme; Leukodystrophy; Disorder of peroxisomal alpha-, beta- and omega-oxidation; Disorders with deficiency of a single peroxisomal enzyme; Leukodystrophy; Peroxisome disorders See More

Summary Summary

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]

Last updated: 2/12/2018

Symptoms Symptoms

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), deafness, fatigue, 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]

Last updated: 2/12/2018

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of metabolism/homeostasis	Laboratory abnormality Metabolism abnormality [ more ]	0001939
Attention deficit hyperactivity disorder	Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ]	0007018
Clumsiness		0002312
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Functional motor deficit		0004302
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Headache	Headaches	0002315
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Leg muscle stiffness		0008969
Progressive hearing impairment		0001730
Progressive spastic paraparesis		0007199
Sensory impairment		0003474
Specific learning disability		0001328
Visual loss	Loss of vision Vision loss [ more ]	0000572
30%-79% of people have these symptoms
Adrenal insufficiency		0000846
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Aphasia	Difficulty finding words Losing words Loss of words [ more ]	0002381
Disinhibition		0000734
Hemiparesis	Weakness of one side of body	0001269
Inappropriate sexual behavior		0008768
Increased circulating ACTH level	High blood corticotropin levels	0003154
Increased intracranial pressure	Rise in pressure inside skull	0002516
Neurogenic bladder	Lack of bladder control due to nervous system injury	0000011
Urinary bladder sphincter dysfunction		0002839
Visual field defect	Partial loss of field of vision	0001123
5%-29% of people have these symptoms
Diplopia	Double vision	0000651
Impotence	Difficulty getting a full erection Difficulty getting an erection Erectile dysfunction [ more ]	0000802
Paralysis	Inability to move	0003470
Percent of people who have these symptoms is not available through HPO
Abnormality of the cerebral white matter		0002500
Alopecia	Hair loss	0001596
Blindness		0000618
Bowel incontinence	Loss of bowel control	0002607
Bulbar palsy		0001283
Elevated circulating long chain fatty acid concentration		0003455
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Hyperpigmentation of the skin	Patchy darkened skin	0000953
Hypogonadism	Decreased activity of gonads	0000135
Impaired vibration sensation at ankles	Decreased vibration sense at ankles Decreased vibration sense in feet [ more ]	0006938
Incoordination	Difficulties in coordination Incoordination of limb movements Limb incoordination [ more ]	0002311
Limb ataxia		0002070
Loss of speech		0002371
Lower limb muscle weakness	Lower extremity weakness Lower limb weakness Muscle weakness in lower limbs [ more ]	0007340
Neurodegeneration	Ongoing loss of nerve cells	0002180
Paraparesis	Partial paralysis of legs	0002385
Polyneuropathy	Peripheral nerve disease	0001271
Primary adrenal insufficiency		0008207
Progressive	Worsens with time	0003676
Psychosis		0000709
Seizures	Seizure	0001250
Slurred speech		0001350
Spastic paraplegia		0001258
Truncal ataxia	Instability or lack of coordination of central trunk muscles	0002078
Urinary incontinence	Loss of bladder control	0000020
X-linked recessive inheritance		0001419

Showing of 54 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2019

Do you have updated information on this disease? We want to hear from you.

Cause Cause

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]

Last updated: 2/12/2018

Inheritance Inheritance

X-linked adrenoleukodystrophy (X-ALD) is inherited in an X-linked manner.^[1] This means that the ABCD1 gene is located on the X chromosome. The X chromosome is one of the sex chromosomes. Each woman has two X chromosomes, and each man has one X chromosome and one Y chromosome. Because men have only one X chromosome, they only have one copy of the ABCD1 gene. If this gene has a disease-causing change, they will have X-ALD.

Women who have disease-causing changes in one copy of the ABCD1 gene are known as carriers of the disease. About 80% of carriers do not have signs or symptoms of X-ALD because they have another working copy of ABCD1. However, about 20% of female carriers have symptoms that are similar to the adrenomyeloneuropathy (AMN) type of X-ALD.^[2]

If a male is diagnosed with X-ALD, it is likely that his mother is a carrier of the disease. However, about 5% of cases of X-ALD are caused by a new genetic change (de novo) in the individual. In these situations, the mother is not a carrier of the disease, and other family members are not at risk to have children with X-ALD. Therefore, when a male is diagnosed with X-ALD, it is important to determine if his mother is a carrier by testing her VLCFA levels or by genetic testing.^[2]

If a woman is found to be a carrier of X-ALD, for each of her children there is a 50% chance that he or she will inherit the change in ABCD1. This means that for each son, there is a 50% chance that he will be affected with X-ALD. For each daughter, there is a 50% chance that she will be a carrier of the disease like her mother.

X-ALD shows a characteristic known as variable expressivity. This means that the exact symptoms of each person with X-ALD can differ, even within the same family. For example, some boys may have the childhood cerebral form of X-ALD, while other members of the same family may have the adrenal insufficiency-only type.^[2] It is not known what causes variable expressivity of the disease to occur. The symptoms cannot be predicted by levels of VLCFA or by looking at the exact genetic change (mutation) in each individual.^[2]

Last updated: 2/12/2018

Diagnosis Diagnosis

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]

Last updated: 2/12/2018

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.

Treatment Treatment

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]

Last updated: 2/12/2018

Prognosis Prognosis

The long-term outlook for people affected by X-linked adrenoleukodystrophy (X-ALD) depends on the exact type of the disease that each person has. The childhood cerebral form of the disease is progressive. Boys with this form of the disease often pass away within a few years of beginning to show symptoms.^[2] The other forms of X-ALD are less severe. The disease for these individuals may be slowly progressive, or it may not affect a person’s lifespan at all.^[2]

It is important to remember that the exact signs and symptoms of a person with X-ALD cannot be predicted by the signs and symptoms of other members of the family. Therefore, the long-term outlook for individuals who have X-ALD within the same family can be very different.^[2]

Last updated: 2/12/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to X-linked adrenoleukodystrophy . Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with X-linked adrenoleukodystrophy . The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for X-linked adrenoleukodystrophy :
Myelin Disorders Bioregistry Project

Organizations Organizations

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

Adrenal Insufficiency United
Toll-free: 1-855-AIUnite (248-6483)
E-mail: contact@aiunited.org
Website: http://aiunited.org/
ALD Connect
c/o Kailey Walsh
Massachusetts General Hospital
175 Cambridge Street
Suite 340
Boston, MA 02114
E-mail: info@aldconnect.org
Website: http://aldconnect.org/
Alex The Leukodystrophy Charity (Alex TLC)
45 Peckham High Street
London, SE15 5EB United Kingdom
Telephone: 020 7701 4388
E-mail: info@alextlc.org
Website: https://www.alextlc.org
Association Européenne contre les Leucodystrophies (ELA)
European Leukodystrophy Association
2, rue Mi-les-Vignes
BP 61024
54521 Laxou Cedex, France
Telephone: 333 83 30 93 34
Fax: 333 83 30 00 68
E-mail: ela@ela-asso.com
Website: http://www.ela-asso.com
Leukodystrophy Australia
PO Box 2550
Mount Waverly
Victoria, 3149 Australia
Telephone: 1800 141 400
E-mail: info@leuko.org.au
Website: http://www.leuko.org.au/
National Adrenal Diseases Foundation (NADF)
P.O. Box 566
Lake Zurich, IL 60047
Telephone: +1-(847) 726-9010
E-mail: nadfmail@nadf.us
Website: https://www.nadf.us
The Adrenoleukodystrophy Foundation
241 Camden Street
Slidell, LA 70461
Telephone: 985-718-4728
E-mail: info@aldfoundation.org
Website: http://www.aldfoundation.org
The Myelin Project
P.O. Box 39
Pacific Palisades, CA 90272
Telephone: 800-869-3546; 806 356 4693
Fax: 806 356 4694
E-mail: info@myelin.org
Website: http://www.myelin.org
United Leukodystrophy Foundation (ULF)
224 North Second Street
Suite 2
DeKalb, IL 60115
Toll-free: 800-728-5483
Telephone: 815-748-3211
Fax: 815-748-0844
E-mail: office@ulf.org
Website: http://www.ulf.org/

Organizations Providing General Support

Do you know of an organization? We want to hear from you.

Learn More 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

Genetics Home Reference (GHR) contains information on X-linked adrenoleukodystrophy . This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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.

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References References

X-linked adrenoleukodystrophy. Genetics Home Reference (GHR). July 2013; https://ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy.
Steinberg SJ, Moser AB, and Raymond GV. X-linked Adrenoleukodystrophy. GeneReviews. April 9, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1315/.
Adrenoleukodystrophy (ALD). Kennedy Krieger Institute. http://www.kennedykrieger.org/patient-care/diagnoses-disorders/adrenoleukodystrophy-ald.
Haldeman-Englert C. Adrenoleukodystrophy. MedlinePlus. October 27, 2015; http://www.nlm.nih.gov/medlineplus/ency/article/001182.htm.
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.
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. http://www.nejm.org/doi/10.1056/NEJMoa1700554#t=articleTop.