The article below reflects the personal opinions of the author(s) and does not reflect the views or opinions of the Perspectives editors or committee, or the National Society of Genetic Counselors (NSGC).
When X-linked adrenoleukodystrophy (X-ALD) was added to newborn screening (NBS) panels in New York in 2013, it marked the first time the condition was identified at birth in the United States. Since then, 43 states have added X-ALD to their NBS programs. The goal was straightforward: identify affected boys before the onset of cerebral disease so intervention could be offered in time to change the course. The recent addition of ABCD1 to the ACMG Secondary Findings (SF) v3.3 list marks another major expansion of its detection. Together, these programs are starting to resemble population screening for ABCD1, identifying individuals at all ages, often long before symptoms appear.
This trend prompts an important question: what does it mean to screen an entire population for a condition in which the most common adult outcome, adrenomyeloneuropathy (AMN), has no disease-modifying therapy?
ABCD1’s inclusion alongside other SF genes highlights this contrast. For GAA (Pompe disease), enzyme replacement therapy can slow disease progression even when initiated in adulthood. For cancer predisposition syndromes, surveillance allows early detection and treatment that can significantly improve survival. For ABCD1, however, surveillance in asymptomatic adults focuses on identifying neurologic changes and managing symptoms as they arise, without altering the underlying disease course.
The genotype-phenotype correlation for ABCD1 remains poorly understood. The same variant can result in childhood cerebral ALD or adult-onset AMN, even within the same family. Approximately 65% of males who avoid childhood cerebral ALD will develop AMN later in life. While hematopoietic stem cell transplantation (HSCT) and, more recently, gene therapy can halt cerebral disease in children when performed early, these interventions generally do not benefit adults with AMN.
From a population-screening perspective, the benefits of early ABCD1 detection are most evident in pediatric cases, where monitoring for cerebral involvement can allow timely intervention. In adults, early detection still has value by shortening a diagnostic odyssey, informing family risk and enabling cascade testing. However, the medical benefit is different. It is not about preventing disease onset, but about anticipating and managing a chronic, progressive condition.
As genomic sequencing becomes more common, we can expect the number of asymptomatic adults identified with ABCD1 to rise. This shift raises broader public health and research questions: How should screening guidelines be adapted for a condition with variable onset and no adult cure? What follow-up protocols balance the need for monitoring with the burden of lifelong surveillance? How do we communicate results in ways that maximize preparedness without creating unnecessary distress?
The expansion of ABCD1 detection into what now resembles population screening offers opportunities to refine policy, education and follow-up systems. It also creates fertile ground for research into the long-term outcomes, optimal surveillance strategies and psychosocial impact of this evolving screening paradigm.
This is part one in my two-part series on ABCD1. Read part two here.
References
- Kemp, S., Berger, J., & Aubourg, P. (2012). X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochimica et Biophysica Acta, 1822(9), 1465-1474. https://doi.org/10.1016/j.bbadis.2012.03.012
- Kornbluh, A. B., Baldwin, A., Fatemi, A., Vanderver, A., Adang, L. A., Van Haren, K., Sampson, J., Eichler, F. S., Sadjadi, R., Engelen, M., & Orthmann-Murphy, J. L. (2024). Practical approach to longitudinal neurologic care of adults with X-linked adrenoleukodystrophy and adrenomyeloneuropathy. Neurology Genetics, 10(5), e200192. https://doi.org/10.1212/NXG.0000000000200192
- Lee, K., Abul-Husn, N. S., Amendola, L. M., Brothers, K. B., Chung, W. K., Gollob, M. H., Gordon, A. S., Harrison, S. M., Hershberger, R. E., Li, M., Ondrasik, D., Richards, C. S., Stergachis, A., Stewart, D. R., Martin, C. L., Miller, D. T., & ACMG Secondary Findings Working Group. Electronic address: documents@acmg.net (2025). ACMG SF v3.3 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 27(8), 101454. https://doi.org/10.1016/j.gim.2025.101454
- Moser, A. B., Jones, R. O., Hubbard, W. C., Tortorelli, S., Orsini, J. J., Caggana, M., Vogel, B. H., & Raymond, G. V. (2016). Newborn Screening for X-Linked Adrenoleukodystrophy. International Journal of Neonatal Screening, 2(4), 15. https://doi.org/10.3390/ijns2040015
Katharina Schwan, MS, MPH, CGC (she/her) Katharina Schwan is a board-certified genetic counselor based in the Bay Area, CA. She is a clinical genetic counselor at Community Health Partners as well as the founder of Swan Health Genetics, a private genetic counseling practice. Her interests include alternative models of providing reproductive health care, expanding access to genetic counseling and testing for underserved and underrepresented individuals, and research at the intersection of public health and genomics.