Here’s a brief timeline from 2010-Present of NUBPL as a novel disease discovery to a growing community:

2010: Australian researchers reported “a strategy of focused candidate gene prediction, high-throughput sequencing, and experimental validation to uncover the molecular basis of mitochondrial complex I (CI) disorders.” They created five pools of DNA from a cohort of 103 patients and then performed deep sequencing of 103 candidate genes to spotlight 151 rare variants predicted to impact protein function.

Two novel genes were discovered in this study – one of them was NUBPL. To read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977978/

In 2017, I was able to find the boy in this study, Patient 1. He is 18 years old and living in New Zealand with him mom.

2012: Dutch researchers set out to identify the mutated gene in a group of patients with an unclassified white matter disorder that shared the same distinct MRI pattern. They used MRI pattern recognition analysis to select a group of patients with a similar characteristic MRI pattern and then performed whole exome sequencing to identify the mutated gene. They then examined the patients’ fibroblasts for biochemical consequences of the mutant protein. Results: This study identified 6 NUBPL patients from 5 unrelated families with a similar MRI pattern. Two sisters from Canada were diagnosed with NUBPL from this study. We are now in contact. We can tell from this research that Patient 5 has exact same mutations as our daughter, but we are not in contact with them at this time. To read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662327/

2013: Ambry Genetics was one of the 1st genetic testing laboratories to offer whole exome sequencing diagnostic services for clinicians, including medical interpretation. At the time a family in California has two daughters undiagnosed, ages 13 and 3, with an unknown white matter disorder. Their doctor recommends whole exome sequencing through Ambry and both girls are diagnosed with NUBPL. A few months after Katherine was diagnosed in 2015, I saw their documentary “The Life We Live: The Spooner Story” on the Global Genes Facebook page. Watch the documentary here.

*That same year (August 2013), at the age of two, our daughter has an MRI after a developmental plateau. Based on her MRI alone, top neurologists thought she had a disease called Infantile Neuroaxonal Dystrophy (INAD). Katherine’s MRI was similar to the patients in the 2012 NUBPL Dutch study, but her grey matter is affected. Doctors never suspected or mentioned NUBPL. Whole exome sequencing confirmed NUBPL in February 2015.

2015: Katherine is diagnosed with NUBPL through whole exome sequencing.

2016: We started a non-profit, NUBPL Foundation, to grow the NUBPL patient community, raise awareness, and fund research into the NUBPL gene.

2016-2019: Whole exome sequencing is becoming more common and affordable; however, there are still barriers. To date, all NUBPL patients have ONLY been diagnosed through whole exome sequencing. As far as the research goes to help clinicians diagnose  patients, the 2012 Dutch study, “NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern” is it. We know that Katherine has NUBPL and does not have this “distinct” MRI pattern. As more patients find us from around the world, we believe there may be some other differences that could help clinicians better diagnosis or at least “think” NUBPL as a possibility.

It takes time, awareness, and a larger patient population to see patterns or outliers. The more we talk about it, make noise, and raise awareness as a community (strength and volume in numbers), the better known it becomes to clinicians and researchers around the world.

Personally, I worry about the child getting an MRI today that’s similar to Katherine’s. It’s highly likely the neurologist does not even know about NUBPL because it’s so rare. Depending on the MRI results, there’s a chance they will find that 2012 Dutch research paper, but if the MRI is like Katherine’s, they are likely to keep searching for more common diseases. They may be facing exhaustive testing over the next year or so before whole exome sequencing will give them a definitive diagnosis. There’s also the NUBPL patient with a mild MRI pattern and/or slight developmental delays. These children may also be misdiagnosed.

In the rare disease world, it is our job to make the doctors aware of the disease. As hard as that is believe, that’s the way it flows. The responsibility falls on the parents to find the patients, grow the community, and push for new research (and fund it). It’s hard for a doctor to take on this responsibility unless they make it their sole focus. Realistically, it isn’t feasible for them if they also have a clinical practice. And as a researcher, it doesn’t make much sense to focus all their time on a disease that affects so few patients. If this disease affects a LARGE population? Yes!

For new clinical research to carry weight, you have to have patients, which is one of the biggest challenges with rare diseases. Slowly but surely, patients are getting diagnosed through whole exome sequencing and finding us. If they do not find us, then it’s hard to fit all of these “puzzle pieces” together to see the larger picture. Something most people don’t understand is there’s not a “central” database for doctors to access to find these patients. They really depend on “published” scientific research, and again, it’s our job to find the patients and push this research. Patient registries are helpful. We are getting close to having enough patients for new clinical research and a natural history study of the disease, which is so important for multiple reasons. Again, we have to fund it through our non-profit or find someone who is wants to fund it.

Our job is to be a lighthouse for other NUBPL families. The light has to reach them so everyone can come together on shore, and that light needs to shine bright enough to reach every corner of the world. Some people don’t know to look for a light; others don’t know they are in the NUBPL boat. Some don’t know why it matters or see the benefit of joining a community. As more families join our community, the brighter our light shines around the world. And the brighter we all shine and grow this community, the brighter the light we shine on understanding this disease and helping future patients.  As you may have recognized, the silhouette of the girl in the logo is pointing to something. She is pointing ahead to the light and flying toward it. She is hopeful and optimistic as she flies alone to join her community. Together, they will push the needle of science forward.