What is Adrenoleukodystrophy (ALD)?
Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 17,000 people. It is an X-linked genetic disease, therefore it mostly affects boys and men. ALD involves multiple organs in the body so it most prominently affects the brain and spinal cord. This brain disorder destroys myelin. Myelin is the protective sheath that surrounds the brain’s neurons. Without the myelin sheath the nerve cells that allow us to think and to control our muscles no longer function correctly. ALD knows no racial, ethnic or geographic barriers.
Photo: Aidan Jack Seeger, 7/21/04 – 4/29/12, ALD
Childhood Cerebral ALD is the most devastating form of adrenoleukodystrophy. This form generally occurs between the ages of four and ten years old. Onset can be seen when seemingly normal, healthy boys suddenly begin to regress. At first, they may simply show minor behavioral problems, such as withdrawal or difficulty concentrating, vision problems, or start to have coordination issues. Gradually, because the disease spreads throughout the brain, their symptoms grow worse. Some symptoms could include blindness, deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to a vegetative state or death, usually within 2-5 years of diagnosis.
How does Adrenoleukodystrophy affect the individual?
Adrenoleukodystrophy is a multi-system disease, but most prominently affects both the central and peripheral nervous systems. The nervous systems are responsible for all of the body’s voluntary and involuntary functions. Damage to the brain results in blindness, seizures and hyperactivity. Other effects include problems with speaking, listening and understanding verbal instructions. Damage to the spinal cord results in the loss of the ability to walk and maintain normal breathing.
The most severely affected tissues outside of the nervous system are the adrenal cortex and the Leydig cells in the testes. Damage to the adrenal cortex results in adrenal insufficiency, or Addison’s Disease. Damage to the testes results in infertility.
The rate of progression depends on what form of the disease the individual has.
Although there is currently no cure for adrenoleukodystrophy, the symptoms can be managed to ensure the best possible outcomes. With proactive, comprehensive medical care the symptoms of ALD can be managed and give the individual the best quality of life possible.
Furthermore, through ALD newborn screening, affected children have the opportunity to benefit from lifesaving treatment.
How do you get ALD and why does it typically impact boys?
Adrenoleukodystrophy is a genetic, or inherited, disorder. If a mother is a carrier of ALD, there is a 50% chance of passing this on to her children. If a father is a carrier of ALD, he will pass this on to his daughter.
Spontaneous mutations are another way a baby can inherit ALD. This means that the mother and father are not carriers of ALD, however, the mutation of the gene causing ALD happens in utero. Spontaneous mutations arise from a variety of sources, including errors in DNA replication, spontaneous lesions, and transposable genetic elements.
Mutations in ABCD1, a gene located on the X chromosome that codes for ALD Protein (ALDP), is responsible for causing adrenoleukodystrophy. This gene functions as a peroxisomal membrane transporter. The transporter is required for the normal turn over, or metabolism, of fatty acids in the brain and spinal cord. Without the transporter, the normal metabolism of fatty acids does not occur. Therefore, the brain and spinal cord undergo demyelination. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid.
The damaged gene that causes ALD resides on the X chromosome. Boys inherit only one X chromosome, which is passed to them from their mothers. Because girls inherit two X chromosomes, one from each parent, the functional copy inherited from their father usually protects female children from the disease. However, females with the mutation are carriers who can pass the disease on to their male offspring. It is possible – but rare for girls to inherit two copies of the mutation from both parents.
Could other children in the family also have ALD?
Yes, if a mother has ALD, there is a 50% chance each of her other children also have ALD. It is crucial if the child is male, they should be tested immediately. If there are other female children they can be tested when they are of childbearing age. Extended family – sisters, brothers, aunts, uncles, nieces, and nephews of the affected parent should also be tested for ALD.
To determine if other children in the family are affected by or carriers of adrenoleukodystrophy, it is best to consult with your genetic counselor or your child’s physician.
You can also request a blood spot card from the Kennedy Krieger Institute. The requisition form may be downloaded here.
Results are available within 7 to 10 days, unless there are special circumstances.
Contact information related to testing:
Kennedy Krieger Institute Genetics Laboratory – Peroxisomal Diseases Section
707 North Broadway
Baltimore, MD 21205 USA
How is ALD diagnosed?
Adrenoleukodystrophy is diagnosed through a blood test. The test analyzes the amount of very long chain fatty acids, which are elevated in ALD. An MRI diagnoses cerebral ALD.
While newborn screening for ALD is available in some states, it is NOT a diagnostic test. Newborn screening can, however, lead to a proper and early diagnosis upon confirmatory testing.
ALD Newborn Screening is currently active in 5 states: New York, Connecticut, California, Minnesota and Pennsylvania. More states are slated to come on board in 2018. If you currently live in a state that is not testing, please contact the Kennedy Krieger Laboratory for a blood spot card.
What are the different forms of Adrenoleukodystrophy?
No matter what form of Adrenoleukodystrophy an individual is diagnosed with, comprehensive medical care is of timely importance. The Leukodystrophy Care Network (LCN) was established to provide individuals with the best quality care at certified, specialized centers across the country.
For more information and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.
Adrenoleukodystrophy, or ALD, is an X-linked metabolic disorder. It is characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. ALD takes several forms, which can vary widely in their severity and progression. Unfortunately, there is no clear correlation of genotype (the type of mutation a patient has) and phenotype (the clinical presentation or subtype).
Childhood Cerebral Demyelinating ALD
This is the most common form of ALD, representing about 45% of all ALD cases. Onset generally occurs between the ages of four and ten years old.
Onset can be seen when seemingly normal, healthy boys suddenly begin to regress. At first, they may simply show minor behavioral problems, such as withdrawal or difficulty concentrating, vision problems or start to have coordination issues. Gradually, as the disease spreads throughout the brain, their symptoms grow worse. Some symptoms could include blindness, deafness, seizures, loss of muscle control and progressive dementia. This form of ALD is characterized by an inflammatory process that destroys the myelin. This causes relentless progressive deterioration to a vegetative state or death, usually within five years of the onset of symptoms.
The AMN phenotype occurs in 45% of people with ALD and generally develops in adults. AMN affects the longest nerve fibers of the spinal cord. These fibers conduct signals from the brain to the legs and the bladder and back to the brain.
Some people experience a variety of symptoms such as pain, numbness or tingling in the legs, mild to moderate weakness of the arms and hands, urinary and bowel disturbances or incontinence and walking and balance problems. These problems begin as a general leg weakness and stiffness and progress to walking difficulty. Some people have more problems with their balance. Leg weakness and balance problems can change the way a person walks. Mobility devices such as canes, walkers and wheelchairs may be needed over time.
The majority of other cases of the disease occur as the adult form, known as Adrenomyeloneuropathy, or AMN. In about half of the sons who inherit the mutated ALD gene, symptoms of the disease do not develop until young adulthood. Because of this, they generally progress more slowly than those with the childhood form of the disease.
Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. As a result, these lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one-third of these patients the central nervous system also becomes involved. These young men undergo the same mental and physical deterioration as the previously described boys. The progress of the disease is slower, usually declining to a vegetative state and/or death in five years or longer.
Addison’s Disease (Hypoadrenocorticism)
Addison’s disease is a disorder of the adrenal gland, and about 90% of boys and men with ALD/AMN develop it. In about 10% of ALD cases, this is the only clinical sign of the disorder.
The adrenal glands produce a variety of hormones that control levels of sugar, sodium and potassium in the body, and help it respond to stress. Due to Addison’s Disease, the body produces insufficient levels of the adrenal hormone, so it can be life threatening. Fortunately, this aspect of ALD is easily treated by simply taking a steroid pill daily (and adjusting the dose in times of stress or illness).
Although women who carry the ALD gene mutation do not generally develop the brain disease itself, some display mild symptoms of the disorder. These symptoms usually develop after age 35. As a result, symptoms primarily include progressive stiffness, weakness or paralysis of the lower limbs, numbness, pain in the joints and urinary problems.
Is there a treatment for ALD?
Through ALD Newborn Screening, affected children have the opportunity to benefit from lifesaving treatment. While treatment through a cord blood/stem cell transplant can slow the progression of the disease, it is not considered a cure. Unfortunately, myelin that has already been damaged cannot be repaired by this treatment. Consequently, it is important for ALD to be detected as early as possible before symptoms begin, ideally through each state including ALD in their newborn screening program.
Adrenal Insufficiency or Addison’s Disease
Approximately 90% of boys with ALD will also have adrenal insufficiency, or Addison’s Disease, which occurs when the adrenal glands do not produce enough of certain hormones. The adrenal glands are located just above the kidneys. Adrenal hormones, such as cortisol and aldosterone, play key roles in the functioning of the human body like regulating blood pressure and metabolism, the way the body uses digested food for energy and the body’s response to stress.
While ALD usually does not present before the age of 3, adrenal insufficiency can present within the first year of life. Therefore, it is extremely important to test blood ACTH and cortisol levels. Adrenal insufficiency can be treated easily by replacing or substituting the hormones the adrenal glands are not making with daily steroids. The dose of each medication is adjusted to meet the needs of the patient.
Problems can occur in people with adrenal insufficiency, who have an illness, suffer an injury or are undergoing surgery or sedation for a medical test. To prevent an adrenal crisis, which can lead to death, the dosage is increased to allow the body to handle the additional stress. People with adrenal insufficiency should always carry identification stating their condition, “adrenal insufficiency,” in case of an emergency, as well as the supplies necessary to administer an emergency corticosteroid injection.
Bone Marrow Transplantation
Once a boy is diagnosed with cerebral ALD, it is crucial to undergo prompt evaluation in order to evaluate eligibility for a bone marrow transplant. Because myelin damage cannot be reversed, it is critical for a boy to undergo bone marrow transplantation at the earliest signs of the disease.
A “Loes Score” is a system used to distinguish how far advanced ALD is, and if they are eligible for transplant. A “Loes Score” of less than 9 and closer to 1 has shown to have the most optimal results when considering bone marrow transplantation.
For a cord blood transplant, stem cells come from umbilical cords that are donated and stored after live, healthy births of unaffected donors. To learn more about donating your baby’s umbilical cord, please visit the Carolina Cord Blood Bank.
The 1992 movie “Lorenzo’s Oil” is based on the true story of the Odone family and their quest to find a cure for their son, Lorenzo, who was diagnosed with ALD at the age of 6. Augusto Odone, Lorenzo’s father, developed an oil to treat Adrenoleukodystrophy.
The oil is still considered experimental and may have some benefit in normalizing the VLCFA (Very Long Chain Fatty Acids), which may prevent the childhood cerebral form of ALD. Lorenzo’s Oil is not helpful for boys that are symptomatic and is best used on boys between the ages of 2-10 who are asymptomatic.
For more information on Lorenzo’s Oil, please click here for an educational webinar on Adrenoleukodystrophy and Lorenzo’s oil conducted by Dr. Gerald Raymond, professor of Neurology and Chief of Pediatric Neurology at Penn State Children’s Hospital in Hershey, PA.
Lorenzo’s Oil is available through WEP Clinical. Please contact:
951 Aviation Pkwy Suite 200
Morrisville, NC 27560
For men with Adrenolmyeloneuropathy, methods of care consist of rehabilitation therapy, symptomatic medications for pain and stiffness, creating a diet and exercise regimen for ideal health. There are also clinical trials for developing medications that may be useful.
For Women Carriers
Diet and exercise have shown to help women with ALD.
The FDA approved bluebird bio’s gene therapy treatment for childhood cerebral ALD on September 16, 2022. Gene therapy is a treatment option for children with cerebral ALD that offers an alternative to allogeneic hematopoietic stem cell transplant, eliminating the need for a bone marrow match. SKYSONA® (elivaldogene autotemcel), also known as eli-cel, is now commercially available at designated treatment centers in the United States.
Bluebird bio’s patient services program, my bluebird support, which is appropriate for both caregivers and clinicians to use, can be reached at: 1-833-888-NEST (6378) Monday–Friday, 8 am–8 pm ET or online at mybluebirdsupport.com.
What if my child was diagnosed too late for a transplant?
If an individual is not eligible for transplant, proactive multidisciplinary care is essential to provide the best quality of life possible. There are a variety of therapies, adaptive equipment, and medications available for this very purpose.
All families and caregivers of individuals affected by Leukodystrophy, whether they qualify for transplant or not, should seek the best quality care through the Leukodystrophy Care Network, or LCN.
The LCN’s mission is to revolutionize the health and quality of life of individuals affected by Leukodystrophies with proactive, innovative, and comprehensive medical care standards and specialized centers throughout the U.S., Canada and eventually the world.
To learn more and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.
What research is being done to find better treatments & a cure for Adrenoleukodystrophy?
The Aidan Jack Seeger Foundation, ALD Connect, United Leukodystrophy Foundation, and Stop ALD are all advocacy organizations committed to funding research for better treatments and a cure for ALD and other Leukodystrophies. To learn more about the groundbreaking research currently underway, visit their websites.
Hunter’s Hope is also committed to funding research for better treatments and a cure for ALD and other Leukodystrophies. To learn more about the groundbreaking research currently underway, visit the Research section of our website.
Additional Resources for Families:
Leukodystrophy Care Network
Hunter’s Hope Foundation – Family Care
Hunter James Kelly Research Institute
Duke Children’s Hospital: Bone Marrow and Stem Cell Transplantation
Aidan Jack Seeger Foundation
United Leukodystrophy Foundation
Additional Resources for Medical Professionals:
A Special Thank You
Thank you to Elisa Seeger from the Aidan Jack Seeger Foundation for the content provided on this page.