X-ALD is a genetic disorder that is a form of leukodystrophy and affects approximately 1 in 15,000 individuals. This disorder mainly affects the nervous system and the adrenal glands by causing demyelination of the nerves in the brain and spinal cord. This impacts the ability of the nerves to relay signals to the brain. Damage to the adrenal cortex also causes adrenocortical insufficiency. This may cause weakness, weight loss, skin changes, vomiting, and coma.
There are four distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, an adrenal insufficiency only form, and a type called asymptomatic. The childhood form typically occurs in boys. Untreated children experience learning and behavioral problems that begin between the ages of 4 and 10 and worsen over time, causing difficulty reading, writing, understanding speech and comprehension, aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. Progression of this disorder can be rapid, leading to total disability within a few years. The life expectancy for this form varies, but without treatment individuals with the childhood cerebral form only survive a few years after the onset of symptoms.
Diagnosing X-ALD is done using a blood spot test. In newborn screening, an analyzer is used to measure a signal marker called C26:0-lysophosphatidylcholine (C26:0-LPC). When this marker is elevated, a second-tier test is used to measure the level of very long chain fatty acids (VLCFA’s) in a baby’s blood. High levels of VLCFA’s may identify cases of X-ALD because build-up of these fats lead to damage of the adrenal glands and nerves. If a VLCFA test comes back positive, testing will move to a confirmatory test that looks for changes in the gene that causes X-ALD (called ABCD1). Newborn screening cannot tell what type of X-ALD a baby will have. There is no cure for X-ALD, but treatment may slow the progression of the disease and relieve symptoms. Treatment may include stem cell transplant, medications, physical therapy, and adrenal hormone treatment. Clinical trials have also shown promise in using gene therapy to treat X-ALD; however, more research is necessary.