X-Linked Adrenoleukodystrophy is a disease that affects approximately one in 15,000 boys in childhood and is usually misdiagnosed or goes undetected by medical professionals until the disease is so advanced that their chances for treatment or survival are minimal. This genetic disease is most often passed on from mothers to their boys while both mothers and fathers can pass it on to their daughters, who will be carriers and patients in later years. Women have a 50% chance of passing it on but fathers will always pass their X-chromosome to their girls and never to their sons. (See AMN page). Without accurate diagnosis, ALD will continue to spread and mystify the medical professionals unfamiliar with the disease and its symptoms.
The X-Chromosome is defective or mutated, which prevents the body from creating a protein that binds to the Very Long Chain Fatty Acids (VLCFA’s). This protein normally allows the VLCFA’s to enter the peroxisome within the cell where they are then broken down into smaller chains. With ALD, the VLCFA’s accumulate and this often leads to adrenal insufficiency and deterioration of the myelin sheath in the brain, causing rapid neurodegeneration. The Myelin sheath is the protective coating of the nerves, very much like rubber coating on electrical wiring. When the myelin deteriorates, the brains sensors basically short out. Messages sent to other parts of the body get lost in translation, so to speak.
One of the most common misdiagnosed symptoms of boys with ALD is ADD/ADHD (attention deficit disorder) when in actuality the information that was previously known vanishes.
Tasks that were once performed effortlessly become difficult. As the demyelination process progresses mobility, vision, hearing and speech also become affected. Often MRI’s performed on boys in the early diagnostic stages will reveal an alarming amount of deterioration of the myelin. It is both amazing and surprising how well they can compensate for these difficulties, which has proven to be detrimental in attaining a proper and timely diagnosis.
At the same time, the body’s automatic response to the disease is to send in more white blood cells to repair the damage to the myelin. This, unfortunately, then causes more harm than good by creating an auto-immune response in addition to the neurodegeneration which causes more inflammation, signaling the body to send in more white blood cells and the vicious cycle continues. This creates an inflammatory response to the demyelination.
Sometimes the disease goes undetected until the child experiences an adrenal crisis, which may impact how quickly the disease progresses. Initial diagnosis at this time is often Spinal Meningitis. Steroids can support the adrenal insufficiency, also known as Addison’s disease. Males usually present with signs of adrenal insufficiency between two years of age and adulthood, but most commonly by 7 ½ years of age. These signs are often misdiagnosed as recurring viral infections and include unexplained vomiting and weakness or coma. There may be increased pigmentation or bronzing of the skin. An alarming 50% of males diagnosed with Addison’s disease will also have either ALD or AMN, yet many endocrinologists do not routinely screen patients with Addison’s for these diseases.
This is a list of symptoms that may be exhibited in ALD boys:
• ADD/ADHD - Attention deficit disorder
• Headaches or migraines - pressure behind the eyes
• Change in skin pigmentation - bronzing or tanning
• Unexplained vomiting - usually no accompanying fever
• Undescended or underdeveloped testicles or genitals
• Seizures - mild to severe
• Strabismus or lazy eye, vision difficulties
• Poor coordination - clumsiness
• Emotional or behavioral problems - increases with progression of disease
• Fatigue - low energy and tires easily
• Deteriorated writing skills
• Slow to heal from injury and/or recover from illness
Early diagnosis is key in treating boys affected with ALD!
Although these symptoms are fairly common in and of themselves, we need to persuade physicians who diagnose one or more of these disorders in a male patient to question whether he may also be affected by some of the other symptoms associated with ALD or if there has been a family history of unknown illnesses or MS. The diagnostic test for ALD is readily available through a simple blood draw which can be drawn at many labs. The test is a Plasma Total Lipid Very Long Chain and Branched Chain Fatty Acids test and costs less than $200.
I hope that this information will not be misconstrued and create panic in parents whose child may be exhibiting one or more of these symptoms, but that it will be of benefit to those who aren’t satisfied with the answers they are getting from their pediatricians.
There are not a lot of options for treatment for ALD at this time. Kennedy Krieger Institute has concluded that Lorenzo’s oil has shown to prevent the cerebral onset of the disease by approximately 5 years. Unfortunately, the FDA has not yet approved it so a child must be enrolled in their study to benefit from this treatment.
Bone Marrow Transplant (BMT) is the only treatment that is available to halt the disease. It is a radical procedure that includes chemo and radiation therapy as well as drugs to protect against host vs graft disease, an immune response to the donors stem cells. New pre-transplant drugs have improved survival rates and statistics show a high rate of success, however, a successful transplant by medical standards doesn’t necessarily represent survival. In some boys with cerebral involvement it may even cause the disease to progress more rapidly leaving boys in a vegetative state post treatment. There is a specific protocal in place to try and prevent this outcome. Since BMT’s haven’t been available for a long enough period of time to determine if it is an actual cure, there is no data that shows the disease will not return in later years at this time.
There is hope for a cure on the horizon through gene therapy. A study is being conducted in France and so far has proven to be successful among the four boys that have been treated so far. This is a much safer treatment option as it utilizes the boys own stem cells removing the risk of host vs graft disease post treatment. This study is backed by a large pharmaceutical company with plans to bring the study to the U.S. in the not too distant future.
Fight ALD along with a handful of other ALD organizations from around the world have created the ALD-AMN Global Alliance to work together in order to be a louder voice on a larger scale.
Our first order of business is to get ALD screening approved for all newborn children. We are working with researchers at Kennedy Krieger Institute who have developed the test along with the Mayo Clinic who are conducting a study for Development and Validation of an Assay to Expand Newborn Screening for X-Linked Adrenoleukodystrophy and other Peroxisomal Disorders. They tested 100,000 blood spots and found 4 that carried the gene. Unfortunately, because it was a blind study those families will not have the benefit of knowing and monitoring their children. That is tragic. But we have moved one step closer to getting FDA approval which will help each state implement the program to test all newborn children.