Katherine Belle was born healthy on July 9, 2011. Although she had minor feeding issues, a milk allergy, acid reflux, slow growth, and multiple sets of ear tubes, she was meeting all of her developmental milestones on schedule. Katherine was a happy baby who appeared seemingly healthy to her family and pediatrician.
When her first-time parents noticed how Katherine held her cup with closed fists and had a slight intention tremor while reaching for toys, they became increasingly alarmed that something much more serious was affecting their daughter.
Katherine’s first MRI was ordered one month after her second birthday and showed a malformation of her cerebellum, the area of the brain that controls balance and regulates movement. This explained why Katherine was (and still is) severely off-balance and unable to walk without assistance. The MRS showed abnormal brain chemistry. Together, the results of these two tests indicated a likely metabolic disorder. Based on her rare MRI findings, a group of pediatric neurologists concluded Katherine likely had a rare genetic disease called Infantile Neuroaxonal Dystrophy (INAD).
Her parents were devastated with grief.
Katherine then underwent genetic testing to confirm the INAD diagnosis, which came back negative and thrust the family into an emotionally and physically exhausting two-year diagnostic journey that took them to several prominent  hospitals, multiple specialists, and included every diagnostic test available. Two skin biopsies, a spinal tap, a genetic eye exam, EKG, and an EEG all came back normal, including genetic tests and blood work.
However, a second MRI performed one year later in June 2014 – a few weeks before Katherine’s third birthday – showed the disease was progressing in her brain and had taken over her brain’s entire balance center, yet nobody knew what was the cause. Despite all the other normal test results, Katherine’s doctors still felt that her MRI was consistent with INAD.
Yet, her parents did not believe this was an accurate diagnosis based on their own extensive medical research, finding other INAD families around the world and not seeing similarities, and seeking a third opinion from an INAD researcher. At this point, just two possible tests remained, a muscle biopsy and whole exome sequencing. They decided to push for whole exome sequencing with the hope that an accurate diagnosis would be made. You can read more about their experience in the New York Times Motherlode article, “When the Diagnosis Is Rare, Parents May Know More Than The Professionals.”
In February 2015, whole exome sequencing results confirmed that Katherine Belle has a rare form of Mitochondrial Complex 1 Deficiency based on mutations to her NUBPL gene. To date, Katherine is one of 11 patients worldwide reported in the literature. And, like Katherine, all NUBPL patients have been diagnosed through whole exome sequencing following a lengthy diagnostic journey. Since this type of mitochondrial disease was only discovered in 2010, it does not yet have an official name, but those affected typically refer to it by the gene name “NUBPL.”
NUBPL is a progressive disease that causes atrophy of the cerebellum, as well as lesions in other areas of her brain, global developmental delay, ataxia, nystagmus, and speech articulation difficulty.
Katherine is in the extension phase of the EPI-743 clinical trial at the National Institutes of Health (NIH), takes a mito cocktail, and does intensive physical and occupational therapies. She turned six in July and started the first grade in August 2017. She loves her family, friends, teachers, inclusive dance classes, horses, riding her adaptive trike, unicorns, princesses, chocolate, iPad games, and her stuffed bunny, Bibi. She’s a happy, funny, sweet girl with the most determined, independent spirit, who never gives up. She falls down multiple times a day, but always gets back up with a smile on her face. She has made great progress with walking and can now take her first independent steps at age six. More than anything, Katherine wants to run and play with her friends and she fights with everything she can to make that dream a reality.
Her parents are racing against time to find a treatment to slow the progression of the disease and save her life. Despite Katherine’s sunny disposition and conquer the world attitude, the harsh reality is she desperately needs a treatment that does not yet exist. Mitochondrial disease has zero FDA approved treatments and typically affects multiple organs of patients, resulting in an early death.
Her parents are on a mission to change that.
Katherine’s mom, Glenda, is a contributing writer for The Mighty Publication, where she advocates for rare and mitochondrial disease. Additionally, her parents’ advocacy efforts have directly benefitted hundreds of Kentucky children with mitochondrial disease. They were the energy behind a 2016 law that prevents insurance companies from denying coverage for medical supplements known as the “mito cocktail.” Kentucky was the first state in the nation to pass legislation prohibiting denial of coverage. Katherine’s dad, Dave, speaks to various local groups and national organizations about appealing insurance denials and legislative advocacy. Glenda and Dave both serve on the Mito Family Advisory Board at the Children’s Hospital of Philadelphia. They are on a mission to fund critical mitochondrial disease research and eliminate the diagnostic and treatment barriers facing other families on a similar journey.
Katherine is one of the faces of rare disease in a nationally traveling art exhibit, called “Beyond the Diagnosis,” which shows the children behind the diseases. She is her parents’ greatest blessing and the embodiment of Shakespeare’s famous quote, “And though she be but little, she is fierce.”
Meet Katherine Belle’s Parents
Glenda is a Mitochondrial and rare disease advocate, co-founder and executive director of the non-profit NUBPL.org, a contributing writer for The Mighty and the regional blog, HerKentucky, and a freelance photographer. She serves on the Board of Advisors for the NGLY-1 Foundation. She attended the University of Kentucky, where she received a Bachelor’s in English and a Master’s from the Patterson School of Diplomacy and International Commerce. She was a civil servant in her former life.
David is the co-founder of the non-profit NUBPL.org and an attorney for Miller, Griffin & Marks, P.S.C., in Lexington, Kentucky, where he concentrates his practice in the area of civil litigation.  He attended the University of Pennsylvania, where he received a Bachelor’s in Finance.  He received his JD from the University of Kentucky.  He was an Associate Editor of the Kentucky Law Journal and was elected to Order of the Coif. When he is not fighting mitochondrial disease and other villains, David spends time with his family and writing for his blog, Bourbon and Slate.
You may contact us via email at nubpl.org@gmail.com.
For more information about NUBPL, please visit NUPBL.org.
HOPE FOR KATHERINE BELLE 
My child has a 4q deletion, often with this changes are seen in the brain, walking is delayed, language is affected profoundly. In our case, a karyotype showed the issue… and knowing what genes were affected helped us realize that she was having some occult issues in coQ10 production that were affecting her. We started supplementing with CoQ10 and saw rapid improvement in her language, not a total cure (didn’t expect one) but a help. Then we added R-lipoic acid, and after some tinkering and experimenting found that if we had her on specifically SmartQ10 from Enzymatic Therapies and GeroNova K-RALA 10 liquid (5 drops is enough for her at 50 pounds!) that her improvements were dramatic in language. She learned to walk at 5 1/2. Her balance is still iffy, but she can run. Most important, she’s stopped losing skills. For a long time before we started supplementing, she would lose a word every time she gained a word, which was heartbreaking.
R-lipoic acid may be a particularly low-risk thing to try. The big advantages include helping protect the cells from metabolic damage, and helping the body make better use of the antioxidants it produces itself. 1 drop of the K-RALA per 10 pounds of body weight is a very low dose that has nevertheless provided huge gains. R-lipoic acid is a very low risk high benefit supplement, worth discussing with your child’s doctor. Shiny has taken as much as 300 mg without ill effects, with a well-absorbed form she’s now only taking about 20 mg.
Our son has Aicardi Goutieres Syndrome (not to be confused with Aicardi Syndrome). After an initial low grade fever that would not go away at 2 months after receiving his 2 month shots, he finally had a CT scan ordered that showed calcification in the basal ganglia. He went through a long period of testing because we were told that he had a metabolic disorder (all tests came back normal). Mother’s intuition told me that we were going down the wrong trail so I kept looking. His CT scan report stated “possible Aicardi Goutieres Syndrome” but the doctors thought it was too rare and unlikely. I did my own research and found Dr. Yanick Crow in Manchester, England. He is the lead researcher for this disorder and was willing to take a look at my son during the US conference at Children’s National Medical Center (held every two years-the 2014 conference should be in October). Our son does not have all the symptoms (no skin problems) of the disorder and is a pretty normal kid despite the fact he does not walk on his own and his communication is still developing. At age 5 years, we finally received the results of the gene testing to confirm the diagnosis. I hope this is helpful, if not leading you to a diagnosis for your daughter, then as a demonstration that your persistence and decision to focus your energy on your daughter will result in answers. All the best.
Laura, I am happy your persistence paid off. We know about children our own children far better than the physicians. We are a critical part of the diagnostic team and most good physicians are willing to listen to our thoughts and concerns. I hope our persistence pays off as well.
Dave
We lost my step brother to this disease in 2004 just a little over a month and half shy of 11 years old. It was the hardest thing I’ve ever dealt with. I still miss him and think of him every single day. It’s a terrible disease but do not lose all hope. My step-sister also has INAD. Her mom was told she would not live to be 9 years old. That amazing beautiful strong young lady will be 23 on October 18th. She is living proof that you can beat the odds. Stay positive, and stay strong!
Missy,
I am very interested in emailing with you if you are interested? You may contact me at gcmccoy1@aol.com (Glenda – KB’s mom). Thanks so much for sharing this post with us.
Complete and total shot in the dark but have they considered Rett Syndrome? I have a friend with a daughter with Rett Syndrome and her story is similar to the progression you describe. Probably not the same thing, just tossing it out there. Blessings!
Robyn – Yes, we agree that it’s similar to Rett Syndrome, but her doctor does not think it’s that. Whole exome will identify it if it is. Thanks!
My daughter is also undiagnosed. She is 4 1/2 years old and was born seemingly healthy, too. She started having FTT and developmental delay symptoms around 6 months old. It took a long time for doctors to take us seriously, and for them to cross off all the ordinary, common problems. We recently completed WES through Baylor. Unfortunately, she is still undiagnosed, but I have hope someday, we will have an answer. I’d love to get in touch with you. 🙂
Andrea,
Thanks so much for your message. You may contact me at gcmccoy1@aol.com. Would love to chat anytime.
Melissa,
Thanks so much for posting this important message for others to view as well. Will stay in touch via email.
I was getting ready for church this morning while reading the article in the NY times and then visited your site here. I’m reeling with all of the thoughts of the similarities between our daughters- difficulty with balance and walking, SPD issues, seizure activity, brain atrophy, significant language delays, fine motor issues, and the list goes on. My daughter, Tyley Sue has been diagnosed with a rare genetic disease, deletion of 11p14.1. We are awaiting a full exome with the possibility if more deletions as well. We found out earlier this year the results of her testing after fighting for answers since she was a few months old. I found a doctor at the national institutes of health in Maryland that was able to help us. We are still not sure if there are some mitochondrial issues as well or not, that is our most unknown area. We know a lot more than before about her deletion and we know so far, she’s the only one with this exact gene sequence deletion. They have taken her stem cells in hopes to find a cure through more research to replace the cells that have inhibited her brain growth- there hasn’t been any brain or heard growth since she was 18 months- she’s now 3 and a half. I would LOVE to connect with you somehow to ask some questions about what all Katherine has and compare information that may help us or you! You can check out Tyley Sue’s Facebook page at http://www.facebook.com/Tyleysue or my blog at http://www.ourfutureheartbeat.com. Of course I provided my email for you too:)
Ashley,
Thanks so much for your message. I have liked Tyley Sue’s FB page (she’s adorable). We are also on FB – http://www.facebook.com/hopeforkatherinebelle. You may also email me at gcmccoy1@aol.com. I would love to chat with you soon.
My son has SYNGAP..he has some of the same symptoms. He did not walk until he was 22 months. He was just diagnosed with absent seizures and is non-verbal. We also had the Whole Exome DNA testing. Good luck to you..Know there is a huge Rare Disease Community out there to support you! 🙂
My daughter, Annalee, is 17. When she was born, all appeared to be normal, however, she seemed weaker than my 2 boys. She met milestones such as crawling and sitting up – but seemed to fall over a lot. When she started trying to walk,. she fell all the time. Drs did an MRI which was basically unremarkable. We were given a diagnosis of mild cerebral palsy – even though they did not feel that was the diagnosis- and began speech, OT and PT. Annalee has balance issues, hypotonia and stuttering, vision issues and tremors. All genetics and metabolic testing was normal. We continued on with therapies for the next few years. My younger sister had been diagnosed with breast cancer and lost her almost 4 year battle. It was then that I decided that someone had to be able to tell me something. Annalee and I went to the Kennedy Krieger Center and to Johns Hopkins in Baltimore. We had a 2nd MRI which showed lesions on the basal ganglia of her brain. It was then that drs did more testing for a metabolic of genetic condition. They tested before and after fasting and determined that she had a mitochondrial disorder. Her alanine levels were off and this is what led to the diagnosis. Annalee went on the mito cocktails of a vitamin mix (C,E,Lipoic acid, etc), carnitine, CoQ10.
She has a shadow at school as she could walk only short distances and used a stroller at school. However, in the 4th grade, she got the flu and it sent her body in a tailspin. She had been sick before but had never reacted this way. She was in the hospital for several days and when we got out, seemed to be doing much better until that night when she started gasping for air. She went back into the hospital – this time ICU- where it was discovered that she had proximal renal tubular acidosis. She was out of school for the rest of the year – almost 3 months – and had to learn how to walk – or toddle as she had before – all over again. She never regained to the strength had before but is still the happiest child I know. She is in special ed and is in her senior year at school. We have had several other tests – one being the exome sequencing – but we have never had the complex narrowed down. Annalee uses a wheelchair at school and a walker – and us – around the house. When I read your notes about falling 25 times a day, I could relate. Annalee still falls – even with us and the walker – however she is 5’2 and weighs 125 lbs now. Physically, it is hard lifting, bathing, etc but she is such a light in our world!
It was very interesting reading about the clinical trial.
Thank you so much for all of your information and I hope that sharing our stories can help!!
Monica Loving
Thanks so much for sharing your story, Monica. I’m curious when you had genetic testing done for Annalee? Katherine’s disorder has only been known about since 2010. Wondering if you’ve ever considered retesting or have result re-analyzed?
I’m so grateful that I have found your page. Our beautiful 8 year old daughter has just been recently been diagnosed mitochondrial Complex 1 deficiency after 6 years of comprehensive tests. We’re still awaiting further genetic investigations to reach a genetic diagnosis and understand the severity.
Reading your article I really can relate to what you’ve been through. We too went through hell from when scarlett started walking as we didn’t have a diagnosis. She’s always struggled with motor skills, fatigue, balance. Everything has basically been a real struggle for her. We felt so helpless as like you say, we were like refugees without a diagnosis. Watching Katherine’s videos moved me so much. Katherine is so strong , determined, happy beautiful girl. You both have given me strength and and inspiration to carry on our journey. Thank you
Thank you so much for contacting us, sharing your story, and touching us with your kind words. “Walk on with hope in your heart, and you’ll never walk alone.” Best, Glenda
I’m glad you are finding answers. If you are trying to get whole genome sequencing, please contact me. I’ll share resources. You can google me to see that I am the mother of a girl like your daughter. Lilly was diagnosed at 15 years with ADCY5-related Dyskinesia (through WGSeq). Please reach out to us so we can support you (as well as any other family who reads this) in this journey, as others have helped us. ggrossman@adcy5.org
Thank you for reaching out. We actually got a diagnosis of Mito Complex 1, NUBPL gene in February 2015 through whole exome sequencing. Now we are funding research and growing our patient community to learn more about the disease and fund the research faster. You can read more about our story and research here: http://thepenngazette.com/hope-for-katherine-belle/
Thanks for clarifying, I must have missed that detail. Feel free to reach out to us if we can help.
Thank you, Gay! In case you missed it, here’s the latest article about our diagnostic journey and research: http://thepenngazette.com/hope-for-katherine-belle/ (I think of it as the update to our NY Times article you shared on LinkedIn). I’ll take a look at your work! Thanks again for reaching out.