Adrenoleukodystrophy (also known as X-linked adrenoleukodystrophy, ALD) is a rare, genetic disorder characterized by the breakdown or loss of myelin – the fatty covering surrounding nerve cells in the brain – and progressive dysfunction of the adrenal gland. As an X-linked disorder, ALD presents most commonly in males and occurs in about one out of every 17,000 births.
Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in terms of onset and clinical severity, ranging from adrenal insufficiency to progressive paraparesis in early adulthood (this form of the disease is typically known as adrenomyeloneuropathy or AMN).
The following is a guide from the Kennedy Krieger Institute for diagnosing and treating ALD, answers to commonly asked questions, and resources available to families and medical professionals:
ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The ALD gene can be passed on to a child from either the mother or the father. If a father passes the gene, then all of his daughters will be carriers, but sons will not have the ALD gene. If a mother passes the gene, there is a 50% chance with each pregnancy that the child, whether a boy or girl, will have the ALD gene. Genetic counseling is strongly encouraged. The exact mechanism of the pathogenesis of the various forms of ALD is not known.
For males, testing is easy and can be completed in seven to ten business days. the test used to diagnose ALD, called the “very long chain fatty acid test,” is definitive for males. For females, that same test is only 80% accurate, so further DNA testing is needed for confirmation.
Prenatal testing is available, with options including chorionic villi sampling (CVS) and amniocentesis. In addition, there are in-vitro fertilization options to ensure that babies do not have the ALD gene. A genetic counselor can discuss these options with you. for test requisitions, see www.genetics.kennedykrieger.org.
Newborns with ALD
If a child is born with the ALD gene, no immediate intervention is suggested. Babies can be breastfed or given regular formula. Monitoring for adrenal insufficiency should begin at the age of 18 months and should include yearly MRIs of the brain.
Childhood Presentation: childhood cerebral x-ALD
Onset of the childhood form of ALD, which is the most severe, affects only boys and generally develops between the ages of 4 and 8 years. Early symptoms can be similar to those of attention deficit disorder (ADD), such as difficulty paying attention, mild confusion or forgetfulness, or difficulty in school, are all potential signs that that the brain has been affected by ALD. If untreated, the symptoms may progress to inability to walk, talk, or eat, and could eventually lead to death. Children need to be monitored by brain MRIs every six to twelve months in order to identify early signs of disease progression.
Adult Presentation: Adrenomyeloneuropathy (AMN)
In the adult onset of the disease, symptoms typically are seen as early as 20 years old and then throughout adulthood. It includes spinal cord symptoms, as well as difficulty walking, muscle spasms, peripheral neuropathy (numbness or tingling in the feet and legs) and bladder or bowel symptoms. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of the brain function, which can be monitored by MRIs.
Women Carriers of ALD
Women carriers of ALD can experience symptoms similar to men with AMN later in life. Symptoms vary in women, but may include walking difficulties, numbness and tingling of feet and toes, and bladder or bowel symptoms. It is rare to see cerebral disease or adrenal insufficiency in women with ALD. Symptoms management is the focus.
At some point, most boys and men with ALD will develop Addison’s Disease (adrenal insufficiency). Although this condition can be life threatening if left untreated, it can be managed with a daily intake of steroids. If Addison’s is identified, patients must be closely monitored by an endocrinologist.