We recently did a fresh new patch for Aidan Has A Posse Patch. Who’s Aidan?
Aidan Jack Seeger was born July 21, 2004 a big, bouncing, blue eyed baby. Aidan was walking by 9 months, met all his milestones and loved playing soccer and chess. Little did we know he had ALD (adrenoleukodystrophy) that was silently ravaging his brain. In the middle of first grade, Aidan started having some vision problems – where we thought he needed glasses. After many doctors visits and finally to a neurologist, who performed an MRI, we learned Aidan had ALD. This was June 2011. We embarked on a mission to save his life and went to the University of Minnesota – where we were told he had damage to his brain, a high Loes score, but was still eligible for a bone marrow transplant. After a second opinion at Duke University in North Carolina, we opted to stay there and Aidan was transplanted on July 21, 2011 – his 7th birthday.
Aidan lost his ability to see and shortly after lost all of his abilities. After 7 months at Duke, we transferred to NYU as this was one of Aidan’s last requests – he wanted to “Go home to Brooklyn”. On April 29, 2012 after 10 long months inpatient, Aidan lost his battle with ALD and our lives were forever shattered.
Exactly 11 months to the day – March 29, 2013 – Aidan’s Law was signed in New York and NY became the first state to start testing for ALD on December 30, 2013.
The fight for newborn screening continues as we try to make every state compliant with the RUSP – the Federal Recommended Uniform Screening Panel.
What is Adrenoleukodystrophy (ALD)?
Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 17,000 people. As it is an X-linked genetic disease, which means, it most severely affects boys and men. ALD involves multiple organs in the body, but most prominently affects the brain and spinal cord. This brain disorder destroys myelin, 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.
Childhood Cerebral ALD is the most devastating form of ALD, it generally occurs between the ages of four and ten years old. 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, including blindness, deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to a vegetative state or die usually within 2-5 years of diagnosis.
What is myelin (white matter) and why is it so important in the nervous systems?
Myelin constitutes the “white matter” of the brain. It consists of fatty acid molecules, and provides the protective covering of the nerve cells, similar to insulation surrounding an electric wire. Myelin is required for the rapid, precise transmission of information to and from neurons throughout the brain and spinal cord. Demyelination is the stripping away of the fatty coating (white matter) that keeps nerve pulses confined and maintains the integrity of nerve signals. This process inhibits the nerves ability to conduct properly, thereby causing neurological deficits. In childhood cerebral ALD, not only do cells undergo demyelination, but there is also an inflammatory response, all of which destroy the brain.
When myelin is damaged, communication is lost during transmission. This results in the loss of voluntary and involuntary functions in the body. Currently there is no known treatment to reverse damaged myelin, although there are options to manage symptoms. Proactive, comprehensive medical care will allow families and caregivers to give the affected individual the best quality of life possible. Furthermore, through ALD newborn screening, affected children have the opportunity to benefit from lifesaving treatment, which can halt the disease.
What causes ALD? And why does the disease typically impact boys?
ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, Protein (ALDP), which 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, particularlycerotic acid (26:0).
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 2 copies of the mutation from both parents.
How do you get ALD?
ALD disease 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, but the mutation of the gene causing ALD happens in utero. Spontaneous mutations arise from a variety of sources, including errors in DNAreplication, spontaneous lesions, and transposable genetic elements.
How does ALD affect the individual?
ALD is a multi-system disease, but most prominently affects both the central and peripheral nervous systems, which 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.
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.
Could other children in the family also have ALD?
Yes, if a mother has ALD, there is a 50% chance of each of her other children also having ALD. This is crucial if the child is male and 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 ALD disease, 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
Phone: +1.443.923.2782
Fax: +1.443.923.2755
How is ALD diagnosed?
ALD is diagnosed through a blood test, which analyzes the amount of very long chain fatty acids, which are elevated in ALD.
An MRI diagnoses cerebral ALD.
Although 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.
If you currently live in a state which is not testing, please contact the Kennedy Krieger Laboratory, listed above, for a blood spot card.
What are the different forms of ALD?
Adrenoleukodystrophy
Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, 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. It is characterized by an inflammatory process that destroys the myelin, causing relentless progressive deterioration to a vegetative state or death, usually within five years.
Adrenomyeloneuropathy
The majority of other cases of the disease occur as the adult form, known as AMN. In about half of the sons who inherit the mutated ALD gene, symptoms of the disease do not develop until young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. 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 5 years or longer.
Addison’s Disease (Hypoadrenocorticism)
90% of boys and men with ALD/AMN have Addison’s disease, a disorder of the adrenal gland; 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. In Addison’s disease, the body produces insufficient levels of the adrenal hormone, which can be life threatening. Fortunately, this aspect of ALD is easily treated, simply by taking a steroid pill daily (and adjusting the dose in times of stress or illness).
Female ALD
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, and 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?
Although there is currently no cure for ALD, it is treatable.
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. This is why it is important for ALD disease 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
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, such as regulating blood pressure; 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 and 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.
Lorenzo’s Oil
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. It has not been demonstrated to offer any benefit, but if used, is best used on boys between the ages of 2-10 who are asymptomatic.
For more information:
- Adrenoleukodystrophy: Biochemistry and management
- The efficacy of Lorenzo’s Oil
- Newborn Screening and Expanded Access: What does this mean for Lorenzo’s Oil?
Dr. Gerald Raymond, professor of Genetic Medicine and Neurology at Johns Hopkins, Baltimore, MD gave an educational webinar on adrenoleukodystrophy and Lorenzo’s Oil.
Lorenzo’s Oil is available through WEP Clinical:
Yasmin Khera
Outreach Manager
951 Aviation Pkwy Suite 200
Morrisville, NC 27560
Mobile: 1 919 454 6467
Office: 1 919 694 5088
Fax: 1 919 822 1701
Email: ykhera@wepclinical.com
Please visit us at wepclinical.com for further information.
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. It is crucial 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 their 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.
For AMN
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 with ALD
Diet and exercise have shown to help women with ALD.
Gene Therapy
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 allogenic 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.
For more information:
bluebird bio: info@bluebirdbio.com
Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy
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.
What is the Leukodystrophy Care Network (LCN)?
Every individual affected by a Leukodystrophy deserves the best medical care possible. It is the mission of the LCN to revolutionize the health and quality of life of these individuals through a network of centers led by family advocates and comprised of world-renowned experts in Leukodystrophies and multidisciplinary care.
The LCN provides exceptional standards of care with an attitude that enhances and celebrates life. Medical providers at the LCN centers are committed to a multidisciplinary approach with patient care as the primary focus. With the affected individual’s abilities and potential in mind, LCN providers are also committed to planning for long-term and comprehensive care for prevention of potential complications.
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