ALDConnect One Page Summaries
What is ALD?
- ALD stands for Adrenoleukodystrophy
- This combined word is made up from – Adreno – Leuko – Dystrophy
- Adreno refers to the Adrenal Glands which are found on the top of each of our kidneys
- Leuko is the Greek word for “white”
- Dystrophy means a medical condition in which part or parts of our body become weaker
- ALD is a genetic disorder which we mainly inherit from our mother as it is X-linked which means that it comes from an X Chromosome. It can be inherited from the Father however they can only pass it on to their daughters. Mothers have two X Chromosomes whilst fathers have one X and one Y *
- ALD is a genetic medical disorder which is caused by a faulty gene (mutation) that cannot complete its task as it should and this causes an abnormally large build up of Very Long Chain Fatty Acids (VLCFAs) in our Adrenal Glands (Adreno), Brain (Cerebral) and Blood Cells. Our brain cells (Neurons) which send messages to our body have a protective white (Leuko) coating on them which is known as Myelin and it is destroyed by the very high amount of these acids which also causes the nerve cells to die
- ALD has a number of forms which can affect both male and female. Cerebral ALD can affect young boys, male teenagers and male adults, however it is mainly found in young boys
- Childhood Cerebral ALD (CCALD) which mostly affects the brains of our children aged between 4-10 years
- Adrenomyeloneuropathy (AMN) is the name that ALD is known by when it affects males from teenhood up to adulthood. It chiefly affects the spinal cord and rarely the brain
- Female ALD is also known as Adrenomyeloneuropathy (AMN) and affects only those mothers that carry the faulty gene. Its symptoms are serious but much less severe than the male form of AMN and can occur from late teens onwards **
- Addison’s Disease is caused by the damaging build up of those Very Long Chain Fatty Acids (VLCFAs) in our Adrenal Glands which stop them making the necessary amount of chemicals ( hormones ) for our body to operate properly. 80% of males with ALD will have Addison’s Disease whilst 10% will actually be diagnosed with ALD because it was identified by their doctor.
*Please refer to Information Brochure How is the ALD Gene Inherited for more detailed information
** Please refer to the information Brochure Symptoms for more detailed Information
How is ALD inherited?
Each person normally has one pair of sex chromosomes in each cell.
- Females have two X-chromosomes.
- Males have one X and one Y chromosome.
ALD is caused by mutations in ABCD1, a gene located on the X chromosome.
- A female with ALD has one good X-chromosome and one bad one.
- A male with ALD will have more severe symptoms of the disease than a female because a male only has one X-chromosome, and that chromosome is a bad one.
How are sex chromosomes passed on to children?
- A baby boy inherits his X-chromosome from his mother and his Y chromosome from his father.
- A baby girl inherits one X-chromosome from her mother and one X chromosome from her father.
How is ALD passed on?
- Since a man with ALD only has one X-chromosome and it is bad, he will always pass it on to his daughters. However, he will not pass it on to his sons, since his sons will only get a Y chromosome from him.
- Half of the time, a woman with ALD will pass on her bad X-chromosome to her children, and the other half of the time she will pass on her good X-chromosome.
The images on the following page reflect this pictorially:
Symptoms of ALD/AMN
ALD symptoms can vary depending on age, gender, and the body tissues affected. The tissues that are most severely affected in ALD are myelin, blood, and the adrenal glands. Not all tissues are affected at the same time in all patients. In the world of genetic disorders, doctors group collections of symptoms into “phenotypes” based on the cells and tissues that are most severely affected by a gene abnormality. Individuals with the ALD gene may have different phenotypes. In ALD, the phenotypes are not mutually exclusive. In fact, it is common for individuals to have more than one phenotype at any given time.
There are 4 primary phenotypes that can occur in MALES with the ALD gene:
- Asymptomatic (meaning no symptoms)
- Adrenomyeloneuropathy (AMN)
- Adrenal insufficiency
- Cerebral demyelinating ALD (cerALD)
- Asymptomatic phenotype
All individuals with the ALD gene are free of clinical symptoms for at least the first three years of life. And some may continue to have no symptoms. But as the diagram shows below, the percentage of asymptomatic men and women decreases with age.
- Adrenomyeloneuropathy (AMN) phenotype symptoms:
- Walking and balance problems
General leg weakness and stiffness progresses into walking difficulty and reduced balance. With the weakening of leg muscles, changes in gait, or how a person walks, becomes noticeable. The use of mobility devices, such as canes, walkers, and wheelchairs may become necessary.
- Pain, numbness, or tingling in the legs
- Mild to moderate weakness of the arms/hands
- Urinary problems or incontinence and bowel urgency or incontinence
- Sexual dysfunction, or the inability to obtain or maintain an erection
- Adrenal insufficiency (Addison’s disease) phenotype symptoms:
Adrenal insufficiency occurs as a result of permanent injury to the adrenal glands. Most men with ALD will eventually develop adrenal insufficiency over their lifespan. Women develop adrenal insufficiency much less commonly. Although it is easily treatable, adrenal insufficiency can be life-threatening if it is not recognized promptly. Symptoms are often non-specific and can include weakness/fatigue, nausea, abdominal pain, and low blood pressure. Darkening of the skin is also common.
Adrenal insufficiency is sometimes referred to as Addison’s disease (based on the doctor, Thomas Addison MD, who first described it). There are many causes of adrenal insufficiency in the general population. ALD is the cause of approximately 33% of all cases of adrenal insufficiency. This means that not all patients diagnosed with adrenal insufficiency have ALD. Nonetheless, all patients with adrenal insufficiency should be tested for ALD (and vice versa).
- Cerebral demyelinating ALD (cerALD) symptoms:
Affected boys’ symptoms may include “spacing out” in school: inattention, deterioration in handwriting skills, and decreased school performance; difficulty in understanding speech (though sound perception is normal); difficulty in reading and understanding written material; clumsiness; visual disturbances and occasionally double-vision; and aggressive or unexplained inappropriate behavior. In some boys, seizures may be the first symptom. Symptom severity varies from patient to patient and is not determined by phenotype. Even identical twins may have different experiences with symptom onset and severity. Other symptoms may include:
- Behavioral problems
- Eye pain/Childhood onset migraines
- Recurring viral infections
- Lethargy, tires easily, clumsiness
- Tanning or bronzing of the skin
- Adrenal insufficiency
- Attention deficit disorder (ADD)
The following diagram shows the likelihood of a male experiencing the symptoms described by phenotype above.
As mentioned above, a male who has symptoms associated with a particular phenotype may later develop other symptoms associated with other phenotypes. For example and as the diagram shows, men around 45 years’ old will likely develop both adrenal insufficiency and AMN symptoms.
There are 2 primary phenotypes that can occur in FEMALES with the ALD genotype:
- Adrenomyeloneuropathy (AMN)
Although cerALD and adrenal insufficiency are less common in women, they can occur and should be appropriately considered. Women experience similar AMN symptoms that men do. However, women generally have fewer symptoms that are less severe and develop later in life.
Although there is no known cure for ALD, there are available medications and therapies to treat many of ALD’s symptoms. With increased understanding of the disease and the development of new therapies, we can look forward to many more in the future.
What Can I do to Stay Healthy?
Current Treatments for ALD
Talk to your health care provider about these potential treatment options. ALD Connect physicians are available for consultation. Please contact firstname.lastname@example.org with questions
- Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) is the only currently approved treatment that can stop the progression of cerebral ALD symptoms. This procedure is typically performed when a patient’s disease is early stage. It has not been proven to be effective if the ALD symptoms are advanced.
- Treatment involves administering stem cells from an unaffected individual to the ALD patient.
- Stem cells may come from a relative, unrelated donor or a cord blood bank
- Here is a link to one website that explains allo-HSCT: http://bethematch.org/Transplant-Basics/
- For patients with cerebral ALD whose disease is too advanced for allo-HSCT, there is palliative care to help them be more comfortable. Some medications may help with symptoms such as seizures, spasms, constipation etc.
- Additionally, there are medications available to help manage symptoms of Adrenomueloneuropathy (AMN) such as incontinence, spasticity, and nerve pain.
- Exercise is important for AMN. ALD Connect has produced a video demonstrating some exercises that may be helpful
Note: It is important to check with the patient’s doctor (and physical therapist, if applicable), on what exercises are appropriate for the patient.*Researchers are investigating potential new treatments for patients with ALD and AMN. A good resource to look for ongoing clinical trials is https://clinicaltrials.gov
-> key word: adrenoleukodystrophy or adrenomyeloneuropathy