Understanding Genetics and Risk in Adrenoleukodystrophy
Babies with adrenoleukodystrophy (ALD) are neurologically normal at birth. Boys with ALD are at risk of developing adrenal insufficiency and/or inflammatory demyelinating brain lesions (cerebral ALD). Newborn screening has revolutionized the diagnosis and treatment of ALD, as it allows for the early identification of at- risk boys and life-saving interventions. These include initiating timely adrenal steroid replacement therapy following detection of adrenal insufficiency, and providing allogeneic hematopoietic stem cell transplantation (HSCT) as a means of treating cerebral ALD.
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 ALD-related disease symptoms, even with older relatives with the same variant. These novel variants are reported as “variants of uncertain significance (VUS)” on genetic testing reports. If a variant has not yet been linked to a specific disease, it is uncertain whether the variant is benign or pathogenic. However, a positive newborn screening result and referral to a medical specialist starts the process of follow-up and periodic testing for adrenal dysfunction and cerebral ALD by MRI.
Our goal is to understand which genetic variants put a male at risk for disease. This is an important project for our patients, families, and physicians. We are collaborating internationally in a joint project for this work and would appreciate 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.