Adrenoleukodystrophy (ALD) is a rare genetic disease linked to the X chromosome. It is caused by a failure of peroxisomal fatty acid beta oxidation, which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. Clinically, ALD presents as a heterogeneous disorder, showing several distinct phenotypes, and no clear pattern of genotype-phenotype correlation. As an X-linked disorder, ALD presents most commonly in males; however, approximately 50% of heterozygote females show some symptoms later in life.

The most severe form of ALD is the childhood cerebral form, which is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. Approximately two-thirds of ALD patients will present with this form of the disease. The other forms of ALD vary in timing of onset and in clinical severity, ranging from adrenal insufficiency alone to progressive paraparesis in early adulthood.

ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid (26:0) .

Symptoms of ALD often begin between the ages of 4 and 10 but can also present much later in life. Symptoms include loss of vision, learning disabilities, dysphagia (difficulty swallowing), seizures, deafness, and more. Adrenomyeloneuropathy is an adult-onset form of ALD that progresses slowly over decades and causes symptoms such as a stiff gait when walking and bladder and bowel dysfunction. Women who are carriers for ALD develop a milder form of the disease during adulthood.

ALD cannot be cured, but treatment can help manage symptoms and slow the progression of the disease. Adrenal dysfunction may be tr...