Adrenoleukodystrophy (ALD) is a genetic disease that usually affects males. The brain disorder destroys the nerve cells that allow us to think and to control our muscles.
What Is Adrenoleukodystrophy?
Adrenoleukodystrophy is an and the nervous system. It is a rare disorder that affects males, leading to the abnormal buildup of fatty acids in the nervous system and adrenal glands, the glands that produce sex hormones and cortisol. The (childhood cerebral adrenoleukodystrophy) presents with cognitive and behavioral abnormalities and progresses to profound neurological damage and possibly death. The adult form (adrenomyeloneuropathy) presents primarily with weakness in the legs, sexual dysfunction, and bladder control problems, and progresses slowly over decades.
If untreated, the childhood form of this disorder can result in death or a vegetative state. Stem cell transplants and gene therapy are both promising in preventing neurologic decline in the childhood form of the disease. The adult form progresses more slowly over decades and may also benefit from gene therapy or other support.
You should visit your primary care physician, who will perform a blood test to rule in the diagnosis. Since this is a genetic condition, no cure is available, but steroids can be used if the adrenal gland is not making enough of its own.
Symptoms of Adrenoleukodystrophy
The symptoms of each of the three types of ALD are described below. The types are childhood cerebral ALD (CCALD), adrenomyeloneuropathy (AMN), and adrenal form.
Boys with this form will present between ages 4 and 8. Symptoms include:
- Learning disabilities
- Behavior problems: The child may be diagnosed with ADHD initially.
- Severe neurologic deterioration
- Adrenal insufficiency symptoms: Such as nausea, vomiting, and muscle weakness. They may also have hyperpigmented skin.
This form presents in adult males between ages 20 and 40. Symptoms include:
- Progressive stiffness and
- Abnormal control of the bladder
- Sexual dysfunction
- Numbness and pain in and
- Adrenal insufficiency symptoms: Such as fatigue, nausea, vomiting, and muscle weakness. They may also have hyperpigmented skin.
- Similarities to the childhood form (CCALD): This includes cognitive or behavioral abnormalities, vision loss, or seizures.
Adrenal form symptoms
This form presents typically by age 10. Symptoms include those of adrenal insufficiency:
- Muscle weakness
- Possible hyperpigmented skin
What Causes Adrenoleukodystrophy?
Adrenoleukodystrophy is characterized as a rare genetic mutation and has no other known causes.
Genetic mutation details
The specific mutated gene, the ABCD1 gene, causes the resulting disease by:
- Protein encoding: The mutated ABCD1 gene encodes the adrenoleukodystrophy protein.
- Poor transport of fatty acids: This protein facilitates transport of very-long-chain fatty acids (VLCFA) into peroxisomes, the organelle in the cell that degrades and recycles fatty acids.
- Fatty acids build up: VLCFAs build up in the nervous system and adrenal glands, causing a spectrum of neurologic and adrenal dysfunction.
Who is most likely to be affected
This mutation is an X-linked disorder, which means females can carry the mutation and may have mild manifestations.However, males are most affected by the disease, approximately one in 15,000.
Treatment Options and Prevention for Adrenoleukodystrophy
For asymptomatic people who have ALD, surveillance with MRI is common. Typically, other treatments are not initiated until symptoms start to occur.
Diagnosis and testing
The reason for you to be tested and the phase of life you are in will determine the testing type and any follow-up required.
- : In the United States, newborn screening is recommended but implementation varies by state. You can see if newborn testing occurs in your state .The screening test looks for high levels of one specific, very-long-chain fatty acid, and is not a definitive test. Infants with a positive newborn screening test need to undergo confirmatory testing.
- Follow-up testing: Follow-up testing involves measuring the level of very-long-chain fatty acids in the blood. This level is elevated in nearly all people with the disorder. If this test is positive, genetic testing should be done to confirm the ABCD1 mutation is present.
- Imaging: Brain imaging is an adjunctive test following diagnosis of ALD. Typically, people with confirmed ALD will have repeat MRIs to image the brain and spinal cord. This is mainly to track progression over time.
- Electrophysiology: Electrophysiology is an adjunctive test following the diagnosis of ALD. These tests look at the function of specific parts of the nervous system. This can help track progress of visual loss, hearing loss, and loss of muscle or sensory nerve function.
Progression and prognosis
The progression and prognosis of this condition varies depending on the form experienced.
- CCALD: If left untreated, 90 percent of CCALD cases progress to total disability within six months to two years, and death within five to 10 years. If treated successfully, survival significantly improves. However, no treatment is curative and symptoms may continue to develop in adulthood.
- AMN: Unlike the childhood form of the disease, symptoms of AMN progress slowly over decades. Most people lose the ability to walk by age 50. There are currently no available treatments proven to slow or prevent progression of the disease.
- Adrenal form: People can be successfully treated with hormone replacement therapy. However, many will begin to develop neurologic symptoms by middle age, and have a similar course to people with AMN.
Treatments to address neurologic symptoms
The following treatments are typically used for CCALD. Unfortunately, they do not work for AMN and they do not address adrenal dysfunction.
- Hematopoietic stem cell transplant (HSCT): People with CCALD are frequently treated with HSCT. In HSCT, you receive blood-forming cells (cells from which all blood cells develop) from a with similar but not identical genetics. Donors are often siblings or parents. The mechanism by which HSCT works specifically in ALD is unclear, but have suggested and survival.
- Gene therapy: Gene therapy involves removing your blood-forming cells, modifying the mutated gene, and replacing the cells. This technique can be used if you cannot undergo HSCT because youdo not havea matched donor. Several studies have also suggested improved neurologic outcomes and survival for people with CCALD.
Treatments to address adrenal dysfunction
The following options specifically address neurologic symptoms associated with ALD.
- Corticosteroid replacement: Adrenal dysfunction or insufficiency in people with ALD is treated effectively with hormone replacement therapy. However, this treatment does not treat the neurologic dysfunction.
- Supportive therapy: Treatment of people with advanced ALD is typically supportive and includes speech and physical therapy. The prognosis for advanced ALD is poor, and involvement of a palliative care team specializing in end-of-life is helpful.
- Other interventions: Various dietary modificationsincluding low-fat diets and a product called Lorenzo's oil have been used as treatment for ALD in the past. However, none of them appear to prevent or slow the progression of disease and are not recommended by experts.
Prenatal testing is available for pregnant women who have children with ALD or other family members with the disease. Other than selecting for an embryo without the mutation, there is no way to prevent this disease.
When to Seek Further Consultation for Adrenoleukodystrophy
If you have ALD in your family or you have been diagnosed with ALD, you should seek expert consultation. It is appropriated to be evaluated initially by a geneticist and a neurologist specializing in ALD.
Questions Your Doctor May Ask to Determine Adrenoleukodystrophy
- Have you lost your appetite recently?
- Any fever today or during the last week?
- Are you sick enough to consider going to the emergency room right now?
- Are you experiencing a headache?
- Have you ever been diagnosed with cancer?
Self-diagnose with our free if you answer yes on any of these questions.
- Adrenoleukodystrophy. Online Mendelian Inheritance in Man. Updated September 9, 2013.
- Moser AB, Fatemi A. Newborn screening and emerging therapies for x-linked adrenoleukodystrophy. JAMA Neurol. 2018;75(10):1175-6.
- Salzman R, Kemp S. Newborn screening. Adrenoleukodystrophy Info.
- Shapiro E, Krivit W, Lockman L, et al. Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet.2000;356(9231):713-8.
- Peters C, Charnas LR, Tan Y, et al. Cerebral x-linked adrenoleukodystrophy: The international hematopoietic cell transplantation experience from 1982 to 1999. Blood. 2004;104(3):881-8.
- Mahmood A, Raymond GV, Dubey P, Peters C, Moser HW. Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: A comparison study. Lancet Neurol. 2007;6(8):687-692.