Private draft — medical review pending. This post shares our family’s perspective and research discussion. It is educational and does not replace advice from your care team.
Back in 2021, I sat down with Stephan Kemp, PhD, an ALD researcher at Amsterdam UMC. I wanted to talk about adrenoleukodystrophy (ALD) and the questions Alison and I were still carrying after Lucas’s newborn screen.
Recorded in 2021. Research and clinical guidance may have changed since then.
When Lucas was identified through newborn screening, Alison and I were trying to understand a disease we had never heard of. We were also told that the genetic variant found in our family was a variant of uncertain significance, or VUS. At the time, we didn’t really know what that meant. We wanted to understand what the result could tell us about Lucas—and what it couldn’t.
That search led us to Stephan. Looking back, there’s one question I keep coming back to: What can we actually learn from an uncertain result?
From DJ to ALD researcher
Before he was studying ALD, Stephan was a youth-center DJ in Amsterdam, playing new wave and punk records. That was one of the first things I wanted to ask him about. How do you go from putting together a playlist to studying a rare disease?
He told me about studying biology, working at the Amsterdam medical center, and finding an opportunity to work on ALD around the time the gene was identified in the 1990s. What started as a research job became decades of work trying to understand the condition.
The more we talked, the more I saw a connection between the DJ and the researcher. In both cases, Stephan was gathering information, finding connections and sharing what he found with other people. It’s a simple comparison, but it helped me understand something about the way he approaches his work.
Why the ABCD1 variant registry mattered to us
Stephan talked about building an online resource to bring together information about changes, or variants, in the ABCD1 gene. He described collecting reports from the scientific literature and laboratories, and adding information from studies that looked at how cells functioned.
Stephan helped launch the ABCD1 Variant Registry with Hugo Moser. For a family or care team trying to make sense of a genetic result, bringing evidence together in one place can be valuable.
But a registry entry is not a prediction of what will happen to a child. A variant may have different kinds of evidence behind it, and some questions remain unresolved. Families should go through their own results with a genetics professional or ALD care team rather than trying to interpret a database alone.
What did the grey zone mean for our family?
When you hear that a result is uncertain, you want someone to tell you what happens next. Is our son at risk? What should we be looking for? Are we going to get an answer?
In our 2021 conversation, Stephan explained that some results don’t fit neatly into an easy answer and that researchers were trying to understand them better. For Alison and me, that was an important conversation. We weren’t looking for anyone to promise that Lucas would be fine. We wanted to know whether more information could help our family and our doctors understand his situation.
A VUS means that the significance of a genetic change is uncertain. It does not, by itself, establish that the change is harmless or that it causes disease. An abnormal newborn screen also needs follow-up; it is not, on its own, a complete diagnosis.
The skin-cell research we took part in
Stephan also talked about studying how cells work as one way to gather more evidence about certain variants. After learning about the research, Alison and I decided to take part, and Lucas’s cells from a skin biopsy were sent to Amsterdam.
For us, participating meant helping with a question we cared deeply about. It did not provide a simple answer to every question about Lucas’s future. Functional testing can add evidence about some variants, but it cannot necessarily resolve every uncertain result or predict how ALD will affect an individual. Decisions about testing, monitoring and care belong with each family’s healthcare team.
What happened after that 2021 conversation?
Nearly five years after we spoke, researchers published a 2026 Grey Zone Project paper. The paper examined biochemical results from males with our family’s variant and family histories, and proposed a lower-risk research category for childhood adrenal insufficiency and cerebral ALD.
That work is encouraging to our family, and there is still more to learn. A proposed research category is not the same thing as an individual prognosis or a clinical reclassification. It doesn’t tell us everything about any one person’s future or about every possible manifestation of ALD.
Those findings came after our 2021 conversation. Alison wrote about what it was like for our family to live with that uncertainty.
Why I wanted to look back
I asked Stephan where he hoped this research could go in five or ten years. What I wanted then is what I still want now: better information for families and doctors, so they can make the most informed decisions possible for each person.
I also think about the people behind that work. Stephan has been kind and generous with his knowledge, and he’s part of a community of researchers, doctors and families who keep asking questions together.
If your family is at the beginning of this, I know how overwhelming the uncertainty can feel. Keep asking questions, find people you can talk to, and bring your own results to your care team. There is still a lot we don’t know, but there are people working hard to learn more.
Related guides: The ALD Grey Zone · ALD newborn screening
Private draft · Medical expert review pending · The Lucas Project Foundation