Adrenoleukodystrophy (NORD)

With adrenoleukodystrophy, sometimes called ALD, adreno- refers to the adrenal glands, while -leuko-, means white, and -dystrophy refers to tissue degradation. So, adrenoleukodystrophy is a rare genetic condition, caused by a mutation in the ABCD1 gene, located in the X-chromosome, that leads to the progressive loss of white matter in the nervous system, and the degradation of adrenal glands. Generally, genes tell our bodies how to make proteins. In this case, the ABCD1 gene directs the body to produce adrenoleukodystrophy protein or ALD protein. ALD protein is a transporter that is found embedded in the membranes of vesicles found in cells that break down specific forms of fatty acids, called peroxisomes. Its function is to import into peroxisomes, a group of fats, naturally present in the human body and in our diets, called very long-chain fatty acids or VLCFAs.

Once inside the peroxisomes, these molecules are broken down into shorter forms of fatty acids. Now, in adrenoleukodystrophy, there’s a mutation in the ABCD1 gene which leads to a defective ALD protein. Without a working ALD protein, VLCFAs have no way of entering the peroxisomes to be broken down, so they accumulate inside cells. This build up of VLCFAs is thought to be damaging to our nerve cells and the glial cells that support them, the cells in our adrenal glands that produce steroid hormones, the cells in the testicles, and some of our immune cells. Adrenoleukodystrophy is inherited in an X-linked fashion. This means that the ABCD1 gene is found on the X-chromosome. Males who carry a ABCD1 gene mutation on their X chromosome will have the condition. 85% of females who carry a ABCD1 gene mutation on one of their X chromosomes present higher levels of VLCFAs and half experience symptoms.