When I volunteered for the PaReNts project back in April, I really wanted to be able to attend the ACD Conference. But at that stage, our family had not yet had COVID and my son with Creatine Transporter Deficiency (CTD) was not yet fully vaccinated. Australia was only just opening its borders to the rest of the world and travel was challenging. We didn’t think getting to the conference was a viable option. I decided I still wanted to volunteer even if I was not chosen and was extremely pleased to be included.
Fast forward a few months. People were traveling more freely, our whole family was vaccinated, and COVID had finally caught up with the Langsworth family. This meant that, really, our immunity was as high as it was going to get and travel suddenly became an option. Due to cost and the lack of snow in Park City during summer, my husband decided he would stay at home with our son.
My first thought from the conference was WOW, there are some smart people working on these issues. Secondly, the science involved is extremely complicated, which explains why it takes so much time and money to find answers. Finally, isn’t science amazing!
Hopefully, you can watch the individual sessions or read the papers. I am not going to try and cover all the presentations; instead, here are some thoughts I had from the conference. As my son has CTD, please excuse that my comments mostly centre around CTD.
Genetic variation and symptom variation
One of my takeaways from the first day was that there is not just one version of CTD. Instead, we are talking about many different genetic variations and perhaps, an explanation of why the symptoms can vary greatly. This also means that potentially some treatments might work for some variations but not for all.
It also struck me how important computer programming, modeling, and data analytics are in this process. This probably should have been obvious. I guess it was not what I previously imagined when I thought of someone working towards a treatment for a disorder. Upon reflection, it is the increased power in computing that has led to many recent advancements in science. Why is this important? I believe it is critical that you have people with different skill sets involved and helping each other – engineers, data experts, scientists, geneticists, doctors, etc.
Patient population, road to diagnosis, and newborn screening
When Carol Chehowah from Xtraordinaire presented that they had 69 families with CTD in France, I was astounded. Their population is significantly smaller than the USA, and yet they had identified far more cases per capita. How/why?
I don’t think that CTD is necessarily more prevalent in France than USA or Australia on a per capita basis. Therefore, it occurred to me that it must relate to the pathway to diagnosis. Until recently, you could NOT get full exome testing in Australia under our public medical system. If you had a development delay, you might get a micro array that included other X linked disorders like Down syndrome, Fragile X, and Angelmans syndrome. But the test did not include CTD. I suspect patients who presented like my son – only seizure linked to illness and clean micro array – were given the diagnosis of intellectual disability of unknown cause or ASD. No further investigation is ever conducted. Most families would not have known they could ask for full exome testing, and even if they did, until two years ago for many the cost would have been prohibitive. I am not sure what the requirements for testing are in the USA, but I expect there have also been cost restrictions. However, it sounds like in France testing is more readily available (at least in major cities) and cost is covered by the health care system.
While there is no perfect test for newborn detection of CTD, one of the presentations explored whether urine testing was possible for newborn screening. In our case, my son’s elevated levels of creatinine in urine after his seizure were dismissed, and it took further 4 years to get diagnosis. It will be interesting to see how many more people are diagnosed as the cost of exome testing has come down and is more widely available (in some instances you can now get this test through our public health system in Australia). We also might see greater variation in the gene mutations and severity of symptoms. Though, I suspect any kids who do not present with seizures may never be picked up in the Australian system because they would never see a neurologist and never get referred for exome testing.
There were great presentations on day 2 about newborn screening. Until recently, I thought newborn screening for GAMT was across Australia, but turns out it is only in Victoria. There is still work to be done to see it brought into more states in Australia. Huge congratulations to ACD on its enormous effort to see this brought in across the USA. You are changing lives!
Ultimately, I am not an expert. So why all this speculation and why do I bring it up? I think it highlights there is a role for education and advocacy for better testing in Australia. One of my takeaways from the conference was how important it is to have an identified patient population and to have natural history data. This is something, as parents, we can be part of and be actively lobbying for better diagnosis/early detection and providing patient history/samples.
Day 2 had more excellent presentations from researchers. I continued to be blown away by the science involved. I recommend you look at the presentations from Session 5 on Day 2 to get the scientific detail.
What are some of my takeaways? That gene therapy is not as simple as adding the coding into a virus and sending it out into the body. There are intricacies in relation to what coding you are inserting. There are complications as to where you can get the virus to circulate in the body.
In relation to CTD, I was very excited to hear Laura Baroncelli’s presentation on her findings. It was sounding very promising that they were able to have cells be able to make the creatine transporter protein. But the fact that the mice were deceased three weeks later from potential inflammation in the brain, not such great news (for me or the mice involved). While, as parents, we would all love a cure now, this is a reminder that unfortunately answers can take time – for appropriate investigation to occur. We are living in a time of incredible emerging science around gene therapy, but it should come with a word of caution. Like many great rewards, it is not without great risk.
It is often said that being a special needs parent is a lonely experience. Many parents report feeling disconnected from community or feel the need to withdraw from “normal” community activities. The conference was a powerful reminder that we are not alone in our struggles. We are part of an amazing community and support network. This for me has been one of the powerful outcomes from finally getting a diagnosis – a chance to participate in a community of people who understand my family. Thank you for welcoming me into your community. I am only sad that we were not able to bring our son. I know he would have loved the chance to participate in camp and make his own connections. Perhaps next time…
In summary, I was interested to see that the issues were being examined from a variety of different perspectives – gene therapy, treatment through use of existing drugs, testing to find patient populations, gathering of natural history and patient registry. I do think it is important to not have one’s eggs in a single basket. Plus, often answers in science come from unexpected places.
I am grateful to have had the opportunity to meet some of the amazing people working on these issues. Please continue your amazing work. As a parent, the answers can never come soon enough!
Recordings from the 2022 Scientific & Patient Symposium are now available and can be viewed on YouTube.