What is ALD?
Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, affecting 1:17,000 people. It is characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. Brain function declines as the protective myelin sheath is gradually stripped from the brain’s nerve cells. Without that sheath, the neurons cannot conduct action potentials—in other words, they stop telling the muscles and other elements of the central nervous system what to do. This sequence of events appears to be related to an abnormal accumulation of saturated very-long-chain fatty acids (VLCFA) in the serum and tissues of the central nervous system, which sets off an abnormal immune response that leads to demyelination. It is unclear exactly how this chain of events works, but scientists do know that it has its roots in genetics.
ALD is caused by a genetic abnormality, commonly referred to as a “genetic mutation”, affecting the X chromosome, otherwise known as an “x-linked” condition. Everyone has two sex chromosomes: women have two X chromosomes and men have an X and a Y chromosome. If a woman inherits the abnormal X chromosome, she still has a normal, second X chromosome to help balance out the affects of the mutation. Boys and men do not have a second X chromosome, so if they inherit this genetic abnormality, they will most likely get the disease.
What is ALD? Adenoleukodystrophy Explained
ALD takes several forms, which can vary widely in severity and progression, which are:
Childhood Cerebral ALD
This is the most common form of ALD, representing about 45% of all ALD cases. Onset of the classic childhood form of ALD, which is the most severe, affects only boys and generally develops between the ages of 4 and 8 years. If untreated, the symptoms may progress to inability to walk, talk, or eat. If detected early, children need to be monitored by brain MRIs every six to twelve months in order to identify early signs of disease progression.
Early symptoms can be similar to those of attention deficit disorder, such as difficulty paying attention, mild confusion or forgetfulness, or difficulty in school, all potential signs that the brain has been affected by ALD.
In adult onset, symptoms typically are seen as early as 20 years old and then throughout adulthood. The adult presentation includes spinal cord symptoms, as well as difficulty walking, muscle spasms, peripheral neuropathy (numbness or tingling in the feet and legs), and possible bladder or bowel symptoms. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function, which can be monitored by MRIs.
Addison’s disease (Hypoadrenocorticism)
90% of boys and men with ALD/AMN have Addison’s disease, a disorder of the adrenal gland; in about 10% of ALD cases, this is the only clinical sign of the disorder. The adrenal glands produce a variety of hormones that control levels of sugar, sodium, and potassium in the body, and help it respond to stress. In Addison’s disease, the body produces insufficient levels of the adrenal hormone, which can be life threatening. Fortunately, this aspect of ALD is easily treated, simply by taking a steroid pill daily (and adjusting the dose in times of stress or illness). If Addison’s is identified patients must be closely monitored by an endocrinologist.
Although women who carry the ALD gene mutation do not generally develop the brain disease itself, some display mild symptoms of the disorder. These symptoms usually develop after age 35, and primarily include progressive stiffness, weakness, or paralysis of the lower limbs, numbness, pain in the joints, and urinary problems.