X-linked adrenoleukodystrophy (X-ALD) is a condition that mainly affects the nervous system and adrenal glands.
It’s more common and severe in males due to how it’s inherited. The nervous system problems come from the breaking down of the insulating covering of nerves in the brain and spinal cord. This breakdown leads to a decline in thinking and movement abilities and, eventually, a shorter lifespan. X-ALD is also linked to adrenal insufficiency, causing a drop in hormone production and issues with blood pressure, heart rate, and fertility.
In males, there are three main forms of X-ALD:
Childhood cerebral form: This is the most severe. Around age 4, kids start having learning or behavior problems, progressing to issues with understanding, speech, vision, hearing, and movement. The symptoms vary in speed but can lead to significant disability within a few years.
Adrenomyeloneuropathy type (AMN): Usually shows up in early adulthood with initial symptoms like trouble walking, speech difficulties, loss of muscle coordination, sexual function problems, and behavior changes. Adrenal insufficiency may also happen, causing weakness, weight loss, skin changes, vomiting, and even coma.
Addison disease only: This is the mildest form, with symptoms of adrenal insufficiency appearing sometime between childhood and adulthood. In adulthood, symptoms of the AMN type might start showing. Female carriers usually have normal adrenal function.
Currently, there’s no cure for X-ALD, but there are treatments to manage many symptoms. Corticosteroid replacement therapy helps with adrenal insufficiency symptoms but doesn’t relieve nervous system issues. A team of healthcare professionals, including neurologists, physical therapists, urologists, eye specialists, audiologists, endocrinologists, and others, is needed for the ongoing treatment and management of individuals with X-ALD.
X-ALD is caused by pathogenic (disease-causing) variants in the ABCD1 gene on the X chromosome and exhibits X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both males (who have one X chromosome and one Y chromosome) and females (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
Approximately 20% of female carriers develop symptoms most closely resembling the AMN type. However, the onset of symptoms in female carriers typically present later on in adulthood.