Understanding Genetics and Risk in Adrenoleukodystrophy
Adrenoleukodystrophy (ALD) is an inherited neurological disease caused by genetic variants of the gene ABCD1. Males with ALD can develop adrenal dysfunction, spinal cord disease, and are at risk for inflammatory demyelinating brain lesions (cerebral ALD), which is often fatal. Females with ALD can develop mild to severe symptoms. Currently, there is no way to predict the clinical outcome of an individual. As we identify more and more different genetic variants of ABCD1, we are unable to even determine which genetic variants put a male at risk for disease for cerebral ALD.
Newborn screening (NBS) has been a transformative shift for ALD. Identifying at-risk boys allows on-going monitoring to treat any adrenal dysfunction and to provide transplant if cerebral ALD occurs. However, in the past five years, newborn screening has identified many boys and families with novel variants of ABCD1 who have no family history of any disease symptoms. The very long-chain fatty acid (VLCFA) levels found with many variants occupy a “grey,” intermediate zone, lower than known pathogenic ALD levels, but higher than controls.
Our goal is to understand which genetic variants put a male at risk for disease, particularly for cerebral ALD. We plan to study whether and how the VLCFA and lipid levels and the genetic variant interact to cause disease. This is an important project for our patients, families, and physicians. We want YOUR help to make this happen.
To learn more about this project, contact [email protected]. We will be happy to talk to you and connect you to the research team.
