ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD Protein (ALDP). ALDP functions as a peroxisomal membrane transporter. The transporter is required for the normal turn over, or metabolism, of a special type of fatty acids in the brain and spinal cord. Without the transporter, the normal metabolism of fatty acids does not occur. Therefore, the brain and spinal cord undergo demyelination. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly - the one that has 26 carbon chains called cerotic acid (26:0).
ABCD1 resides on the X chromosome. Boys inherit only one X chromosome, which is passed on from mom. Because boys only have one copy of the gene, when it is mutated, they become susceptible to ALD.
Girls inherit two X chromosomes, one from each parent. The functional copy inherited from dad usually protects female children from the disease. Females with the mutation are traditionally referred to as “carriers”, and can pass the abnormal X chromosome on to offspring. Importantly, the field is evolving, and we are now starting to find that some women experience neurological symptoms later in adulthood. It is possible – but very rare – for girls to inherit 2 copies of the mutation from both parents.