Katherine Belle was born healthy on July 9, 2011, and she developed normally for the first year of her life. But when she wasn’t walking at 18 months, she began physical therapy to help her learn to walk. Around this time, Katherine also exhibited signs of Sensory Processing Disorder (SPD). This meant that everyday activities such as taking a bath, playing with sand, or sitting on a grassy lawn were overwhelming for Katherine, so she began occupational therapy as well.
When she turned two in July of 2013 and was still unable to walk, Katherine’s pediatrician referred her to be evaluated by neurologists at Cincinnati Children’s Hospital. After observing Katherine and noting a lack of balance and coordination (ataxia), low muscle tone (hypotonia), mild intention tremors (for example, her hands tremble slightly if she reaches for a toy), and gross motor regression (meaning she was standing on her own less frequently), the pediatric neurologists ordered an MRI and an MRS of Katherine’s brain.
The MRI 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. The doctors in Cincinnati concluded Katherine likely had an incredibly rare genetic disease called Infantile Neuroaxonal Dystrophy (INAD). INAD is an inherited neurological disorder that affects axons, which carry messages from the brain to other parts of the body. It is known to cause progressive loss of vision, loss of motor control (including loss of previously acquired skills such as crawling and sitting), and deterioration in speech. There is no known cure for INAD and no known treatment that can stop the progression of the disease. Life expectancy for children with INAD is between 5-10 years of age.
We were sick with devastation.
Katherine then underwent genetic testing to confirm the INAD diagnosis. We were relieved when the test came back negative, indicating that Katherine did NOT have INAD. However, we were cautioned that it is possible in a small percentage of cases to receive a negative test result but still to have INAD. Following the genetic testing, we transferred Katherine’s care to The Cleveland Clinic, and over several months she underwent various tests as we attempted to further rule out the INAD diagnosis. Two skin biopsies, a spinal tap, an eye exam, and an EEG (which detects abnormalities in brain wave patterns) all came back normal. However, a second MRI performed in June 2014 – a few weeks before Katherine’s third birthday – showed the disease is progressing in her brain and has now taken over her brain’s entire balance center. Despite all the other normal test results, Katherine’s doctors at The Cleveland Clinic felt that her MRI was so consistent with INAD that they did not know what else it could be.
Receiving all those normal test results had built up our hope that she did not have INAD, so to be told “INAD” again was more devastating than we can find the words to express. In July 2014 we sent all of Katherine’s test results and medical documentation to Dr. Susan Hayflick in Oregon. Dr. Hayflick specializes in and researches only INAD. We decided to consult with Dr. Hayflick for a third opinion before allowing our hearts and minds to accept this death sentence of a diagnosis. To our surprise, Dr. Hayflick’s opinion is that it is unlikely Katherine has INAD. According to her, INAD patients do not normally show progression in an MRI the way Katherine does. Although many of Katherine’s symptoms are very similar to those occurring in INAD patients, ALL of the testing we have done so far – including, apparently, the MRI – have given results inconsistent with INAD.
Though we take some very cautious comfort in Dr. Hayflick’s opinion that Katherine is unlikely to have INAD, as of now we are still without a diagnosis, even after a year of extensive testing under the care of some of the best doctors in the country. And so our quest for a diagnosis for our three-year-old daughter continues, while the unknown disease progresses in her body. Our next step is Whole Exome Sequencing through GeneDx, which is essentially a comprehensive and thorough genetic test. We are currently in a study at the University of North Carolina – Chapel Hill and will get those results around July 2015. It is apparent that Katherine has a rare metabolic disorder, meaning that somewhere in her genetic makeup, something is coded abnormally. This abnormal coding causes her symptoms – her lack of balance, her inability to walk, her intention tremors, the progression in her brain. We just do not know where in her genes this abnormality exists. We already did one genetic test that indicated Katherine’s abnormality does not exist on the gene known to cause INAD. By doing Whole Exome Sequencing, we hope to find where the abnormality exists. If we can pinpoint that, we may be able to reach a diagnosis or at least perhaps get further answers. Right now, without a diagnosis, we do not even know what we are dealing with. Ultimately, it is possible that Katherine could be a unique case, and that doctors and researchers could conclude she has a metabolic disorder unlike any ever seen before in anyone else.
February 2015, whole exome sequencing results through GeneDx revealed that Katherine Belle has a rare form of Mitochondrial Complex 1 Deficiency based on mutations to her NUBPL gene. (We have been told that there are between 20-50 confirmed patients – ALL diagnosed through whole exome sequencing, and we believe this number will continue to grow with increased testing). The mutations from us differ, Dad’s being a known disease causing mutation and Mom’s being a rare and likely disease causing mutation. What these particular mutations mean in combination is something we do not yet know. Her case looks odd since the gray matter is affected, while these mutations typically cause white matter abnormalities.
The relief of knowing Katherine’s disorder cannot be overemphasized. No one should be in the dark about what is affecting them or their child, yet half of rare disease patients are in this very position. It must change. Increased exome sequencing and research will help us unravel our genetic code and provide answers and treatments for the good of all. This is the future of medicine. Our prayers go out to the entire undiagnosed community.
We will continue to share our journey to help spread awareness about rare diseases, to connect with others in similar situations, and to tell the world about our daughter, Katherine Belle. We hope you will share our story with others, as a chance connection may be what leads us to others with the same diagnosis, which will help us find our “community” and push for treatment.
Katherine is our life’s greatest blessing. Thank you for following us on this journey.
Glenda is a Mitochondrial and rare disease advocate, creator of 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 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 rare disease and other villains, David spends time with his family and writing for his blog, Bourbon and Slate.
Click here to make a donation on Katherine Belle’s gofundme page.
For more information about NUBPL, please visit NUPBL.org.