Frequently Asked Questions
- How does ALD affect an individual?
- Why does the disease typically impact boys?
- Could other children in the family also have ALD?
- Are women only carriers or do they have ALD?
- Who should be tested for ALD?
- What is myelin (white matter) and why is it so important in the nervous systems?
- What is the prevalence of ALD?
- How do you get ALD?
- Are there any treatments?
- What causes ALD?
How does ALD affect an individual?
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.
Why does the disease typically impact boys?
Could other children in the family also have 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.
Are women only carriers or do they have ALD?
Who should be tested for ALD?
Depending on the affected person’s gender, family relationship, and the carrier status of the affected person’s parents, aunts, uncles, and cousins may be at risk of being carriers or being affected.
Testing of at-risk female relatives for carrier status is a two-step process. Measurement of plasma concentration of VLCFA is performed first; if abnormal, the female is affected. Because around 15% of women with ALD have normal plasma concentration of VLCFA, molecular genetic testing should be used to test those females with a normal concentration. Your doctor or genetic counselor, can suggest commercial companies that can perform the required genetic testing.
What is myelin (white matter) and why is it so important in the nervous systems?
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 (see Treatment Section).
What is the prevalence of ALD?
How do you get ALD?
Fig 4: (Left) If a woman is a carrier for the defective ALD gene she has the following possible outcomes with each newborn: when the child is a daughter, there is a 50% chance that the daughter receives the defective ALD gene and a 50% chance that the daughter is unaffected. In case the child is a boy, there is a 50% chance that the son has ALD and a 50% chance that he will be unaffected. (Right) For an X-linked disorder, such as ALD, if an affected man has children, then all of his sons will be free of the disease, since the father always passes his Y-chromosome on to his sons. However, all of his daughters will inherit the defective ALD gene (he always passes his only (affected) X-chromosome on to his daughter).
Are there any treatments?
However, for the most serious phenotype, childhood cerebral ALD, there are potentially lifesaving procedures available. In boys and adolescents with early-stage cerebral ALD, hematopoietic stem cell transplantation (HSCT) can stop the progression of the degradation of the myelin in the brain if the procedure is performed at a very early stage of the disease. After intensive chemotherapy, HSCT relies on bone marrow stem cells from another person who “matches” the patient.
The procedure aims to use the donor-derived cells to produce the protein that the recipient is incapable of making. Unfortunately, this procedure comes with a significant amount of risk. Infections, graft versus host disease, and other complications can be life threatening. HSCT can be lifesaving, but it is not a cure. Research suggests that patients who undergo HSCT as a child may still develop signs of AMN in adulthood.
Gene therapy offers a promising therapy to stop the progression of demyelination without some of the risks HSCT presents.
What causes ALD?
When the VLCFAs build up in the central nervous system, they eventually destroy the myelin sheath—the protective, insulating coating—that surrounds the nerves. This often leads to neurologic problems. VLCFAs are also toxic to adrenal gland cells. The toxicity leads to those cells malfunctioning, which then causes adrenal insufficiency.