A little over two years ago, we received Katherine’s results for Whole Exome Sequencing (WES), giving us a name, NUBPL, to the disease that was a mystery to her doctors and is responsible for the atrophy of her cerebellum. Although we finally knew the name of the mutated gene, and that it was considered a rare form of Mitochondrial Complex 1 Deficiency, we didn’t know much more than that. In fact, at the time we quickly learned that her disease was recently discovered.
Although we were elated to receive a diagnosis, we realized that we didn’t know how the disease would affect Katherine’s life. Her doctor had never seen another patient with NUBPL, so he didn’t have much to tell us in terms of disease progression.
We searched the Internet looking for any information we could find, which included a couple of scientific articles citing six patients from 5 unrelated families. From these articles, we learned more about the patients, including sex, age, country of origin, clinical signs, MRI details, when and if they walked independently, and cognitive function. We had no way of contacting any of these families without knowing their names or doctors. We didn’t even have a photograph.
I felt like a detective scouring the Internet hoping to find a clue. I started tagging everything we shared with “NUBPL” and searched the Internet several times a day for a signal from anyone out there who had this disease. I posted in Facebook groups and wrote blog posts, anything I could think of that might put us in contact with another family with this same disease.
Just a few weeks later, I was looking through posts on the Global Genes Facebook page when I noticed a post from a mom sharing a link to a documentary about their 14-year journey to a diagnosis for both her daughters who were diagnosed with NUBPL. As I watched the documentary, tears rolled down my face as I picked up the phone to call Dave to tell him I’d found another family. And that they looked happy and one was walking independently. After living with a misdiagnosis for nearly two years of a quickly fatal disease, I’ll never forget the moment that I saw the smiling face of a 16-year old girl with same disease as Katherine.
Everything is about perspective in this life. After being told that my child was going to die by the age of seven, that first glimpse at Cali Spooner’s face added years to my child’s life. In her photograph I saw Katherine smiling back at the camera. For the first time, I saw Katherine as a teenager.
And then I saw Ryaan Spooner’s face and recognized my Katherine in her as well. And she could walk independently. Their body types were even similar.
I got off the phone with Dave and contacted their mom, Cristy, who responded immediately and we’ve been in contact ever since. She put us in touch with their doctor at UC-Irvine, Dr. Virginia Kimonis, who was growing fibroblasts to learn more about the disease. We contacted Dr. Kimonis and sent Katherine’s skin biopsy for research.
Last week, our family traveled to California to attend the first NUBPL Family Conference at UC-Irvine and to spend time with the Spooner Family.
We heard from several researchers and toured the lab where they have been growing our daughter’s fibroblasts.
And a few days later, we were able to introduce our girls to one another for the very first time.
Both of our families instantly hit it off as we watched our girls play together. We were all sad that the night had to end and we had to go back to living on opposite coasts.
Katherine and Ryaan share a love of dolls and both are fiercely determined and independent. They are very similar in many ways. Katherine watched Ryaan walk independently, which she learned to do at Katherine’s age (they are two years apart). After seeing Ryaan walking, Katherine is now determined more than ever that she’s going to do the same. And I know she will.
Our girls are three of 11 NUBPL patients identified in the world. After spending time with The Spooner Family, I am reassured more than ever that we will find more NUBPL families in the future. These things take time and we are just getting started.
We are two families brought together through science, hope, love, and a fierce determination to give our girls the best chance possible at life. Where science hasn’t caught up, we will fund the research ourselves through our non-profits. Where there are barriers to diagnosing more patients in the future, we will spend our time to eliminate those barriers. And when we cannot find those patients as they are diagnosed, we will do everything we can to make sure they can find us.
As our families were spending time together in California, a mom with two daughters made contact with both of us. Yes, I am hopeful that we will grow our NUBPL community.
Last year we founded the NUBPL Foundation to elevate NUBPL awareness and research. In February 2015, our daughter was diagnosed with a recently discovered form of Mitochondrial disease named after the affected nuclear gene, nucleotide-binding protein-like (NUBPL). As one of 11 identified patients in the world, research is needed to understand more about this disease.
This is an exciting time for our family as we expand our rare disease journey to grow NUBPL’s patient population and fund research and, hopefully, develop a treatment or cures.
Coordinated by Dave’s cousin, Brian Shemwell, founder and president of the Paducah Bourbon Society, Haymarket Whiskey Bar, Masonic Homes of Kentucky (event food sponsor), and five regional bourbon societies – Louisville, Paducah, Owensboro and Lexington Bourbon Societies and JB’s Whiskey House of Nashville – came together under one umbrella to support our cause, raising a total of $32,000 in ONE night for the NUBPL Foundation from rare bourbon tastings and silent auction items.
Dave and I were blown away by the level of support we received from event sponsors and attendees. As Dave concluded his speech about our rare disease journey and the NUBPL Foundation, he concluded with these words:
“Whiskey is a Celtic word meaning ‘water of life’ and it’s never been more fitting than this moment. Tonight we raise our glasses of whiskey to save a life. To life.”
NUBPL is a form of Mitochondrial Complex 1 Disorder. Discovered just a few years ago that mutations of this gene are disease causing (our five year old daughter has two mutated copies of her NUBPL gene – one mutated copy from mom, one mutated copy from dad), our family wants to know more so our daughter can have treatments and/or a cure.
The bottom line is that we need to fund the research. Researchers need money to study diseases. We founded our very own non-profit, NUBPL Foundation, to do just that. NUBPL Foundation is an all-volunteer (we do all of the work ourselves and for FREE!) non-profit with the mission to elevate NUBPL research and awareness. Simply put, we are raising money to fund research and find other patients with this disease.
We are starting at ground zero with this research. The good news is there are scientists and physicians who want to perform this research, but they need money. For starters, we need to raise $50,000 to purchase a mouse. There has already been NUBPL research performed on plants, but now we need to see what happens when a mouse has NUBPL. There is much to learn from a NUBPL mouse. What is learned from the mouse will determine what comes next.
Rare Bourbon for Rare Disease is our first NUBPL Foundation fundraiser on Saturday, February 25, 2017, at Haymarket Whiskey Bar in Louisville, Kentucky.
This is your opportunity to taste bourbon from a bygone era – a 1982 O.F.C. vintage-dated bourbon – and fund rare disease research at the same time. Only 50 bottles of this very rare bourbon were ever bottled, placing each bottle’s worth at $10,000. Buffalo Trace released all 50 in 2016 to charities for fundraising. One recipient was The NUBPL Foundation. (For more information, click here.)
The NUBPL Foundation, Inc., is a 501c (3) corporation, funding research for a very rare Mitochondrial disease caused by mutations in the NUBPL gene. This disease causes progressive atrophy of the cerebellum in affected children, among other dire complications, and mutations of the NUBPL gene have also been linked to Parkinson’s disease. The hope is that further research will lead to life-enhancing, life-saving treatments for both NUBPL and Parkinson’s patients.
Be a part of bourbon history while supporting an important cause. Join the NUBPL Foundation and 5 Bourbon Societies – Paducah Bourbon Society, Owensboro Bourbon Society, Lexington Bourbon Society, The Bourbon Society, and JB’s Whiskey House of Nashville – at the legendary Haymarket in Louisville. All ticket holders will enjoy light appetizers provided by our event food sponsor Masonic Homes of Kentucky, Inc.
There will be three tiers of entry:
Tier 1 – $250 Donation: (Quantity available: 50)
-1 Flight of 4 Rare Bourbons, including OFC Vintage 1982, 20 Year Pappy Van Winkle distilled by Stitzel Weller, a 20 year Willett Family Reserve (barrel C43A), and a 1971 Old Grand Dad.
-1 Bottle of a Special Knob Creek Single Barrel Private Selection
Tier 2 – $100 Donation: (Quantity available: 50)
-1 Flight of 3 Rare Bourbons, including AH Hirsch 16 year, a 21 Year Old Willett Family Estate (barrel 3936, Liquor Barn Holiday Selection), and a 1970s Ancient Ancient Age.
-1 Bottle of a Special Knob Creek Single Barrel Private Selection
Tier 3 – $50 Entry Donation: (Quantity available: 100)
-1 Bottle of a Special Knob Creek Single Barrel Private Selection
Fred Noe, Master Distiller and 7th generation Jim Beam family member, will attend the event from 7-8:30 to sign bottles of the Knob Creek.
This event will also include a Silent Auction, featuring E.H. Taylor Sour Mash, E.H. Taylor Tornado, 2012 Angels Envy Cask Strength, and multiple years of Pappy Van Winkle.
Other items, available via an on-site raffle or live auction, will include gift baskets from Jim Beam, Sazerac, and Four Roses, special bottles of Private Selections from participating bourbon groups, and other donations from bourbon groups.
Today, our beautiful Katherine Belle turns four years old. Looking back, we realize that every prior birthday has greeted us with worries. By her first birthday, we knew something was wrong; our expectation that she would walk prior to turning one proved untrue and her motor development had stalled. Our nagging worry at one was a gut wrenching terror by two; she still was not walking. On her third birthday, we were living under a death sentence and the day was a bittersweet reminder that we probably had few such occasions left. Today, we have a new – an accurate – diagnosis, NUBPL, Mitochondrial Complex 1, and a new hope. This is a happy day and one of many more to come.
Gene Name: NUBPL, acronym for Nucleotide-binding protein-like
Also Known As: Iron-sulfur protein required for NADH dehydrogenase or IND1
Location: Chromosome 14q12
Symbols: NUBPL; IND1; huInd1; C14orf127
Genetic Inheritance: Recessive
Gene Function: It is an iron-sulfur (Fe/S) protein that, in humans, is encoded by the NUBPL gene. It that has an early role in the assembly of the mitochondrial complex I assembly pathway.
Mutations in the NUBPL gene may cause a rare form of mitochondrial complex I disorder.
Typical clinical signs and symptoms:
Age of onset 1-2 years old
Developmental delay: Some patients
Delay: Motor; Unable to walk
Speech: Abnormal (Dysarthria)
Eyes: Strabismus; Nystagmus
Ataxia: Trunk & Limbs
Cognitive: Normal or Reduced
Other organs: Normal
Course: Progressive, continuous or episodic
MRI: Leukoencephalopathy with abnormal:
Cerebellar cortex: Progressive
Cerebral white matter, deep: May resolve
Corpus callosum: May resolve
*Although these are characteristic MRI findings, there are others including abnormalities in the grey matter of the cerebellum, as is discussed in Hope for Katherine Belle.
Lactate: Serum normal or high; CSF normal or high
NUBPL protein: Reduced
Histology: Ragged red fibers; No COX- fibers
Biochemistry: Complex I deficiency
Overview of NUBPL Mutations
GeneDx (USA): c.166G>A (maternal); c.815-27T>A (maternal); and c.693+1G>A (paternal)
The more we connect with other NUBPL families, the closer we get to finding a cure. Do you have NUBPL or do you think you may? Or, are you a researcher who is interested in studying NUBPL? Please contact us. We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.
NUBPL.org is a patient-run web site created for parents, doctors, or researchers who may know individuals with NUBPL. The more patients, the greater our sense of community, resources, and research opportunities to find a cure. Contact: email@example.com or NUBPL.org.
February 2015 – Katherine Belle was DIAGNOSED through Whole Exome Sequencing: Mitochondrial Complex 1 – NUBPL Gene.
We want to introduce you to the Spooner Family and their daughters Cali and Ryann, both of whom have mutated NUBPL genes like Katherine. We were undiagnosed for only two years…their oldest daughter was undiagnosed for thirteen years.
Although not identical, I can tell you that after seeing this video I immediately saw similarities between our daughters. After being misdiagnosed for so long with something that didn’t feel right in our hearts, it is so comforting to know and accept the correct diagnosis.
Please watch this video when you get some time. It’s lengthy, but very important and inspiring: The Life We Live
We are all interested in finding others with the same diagnosis. They may contact me at firstname.lastname@example.org.
If truth be told, my bond with Katherine came about slower than Glenda’s. In my defense, she had ten months of bonding while Katherine was in utero (whoever said it was nine months is a liar). And, if Katherine’s own childhood is any indication, Glenda also had a lifetime of practice nurturing baby dolls, changing their diapers, dressing them, feeding them and tucking them into bed with sweet kisses and “night-nights,” groundwork for this specific mother-child bond.
As for me? Well, before Katherine, I had zero experience changing diapers, dressing, feeding or holding an infant. My “doll” experience consisted of Mego Hulk smashing Mego Superman over the head with my sister’s doll house in an epic battle for the ages – or at least the most epic battle since yesterday’s.
As far as the pregnancy part of fatherhood was concerned, I spent it with a feeling of complete uselessness and “getting-in-the-way-fullness.” Then, suddenly (or so it seemed to me, though an eternity to Glenda) there Katherine was, screaming at me.
She seemed so small and fragile – except for the screaming at me part, which seemed large and dangerous. She quickly let me know that my ten months of uselessness were not ending with her birth, just taking on a new form.
It seemed wholly irresponsible of the hospital, but after a day or so, they sent this little stranger home with my recovering wife and me. I hoped that “rear her to be President and Nobel-laureate” was the standard Glenda was setting for her care of Katherine, but my personal standard of care at this time was “just keep her alive.”
Don’t get me wrong, I would have run into a burning building to save Katherine from the moment she was born, but, as I said, our true bond had to develop. At first, we were strangers looking at each other; me trying to figure out what to do, and she trying to figure out where mommy went and why mommy had left her with this well-meaning boob (and not the kind that then dominated Katherine’s thoughts).
I cannot tell you when the bond was formed, but I can tell you the moment I realized it had. I was changing Katherine’s diaper and making funny faces at her, hoping for a grin. Then she laughed. Not an “is it gas” smirk, but a full-on belly laugh. The kind of laugh Glenda has (for the record, Glenda does not have an “is it gas” smirk, only a full-throated laugh). I literally jumped in the air out of excitement (I use “literally” correctly here, as I did, in fact, jump). I had heard and made an angel laugh. I called my wife, who didn’t understand my excitement. It was just a typical day to her, but I was struck by the knowledge that at some point during those early sleepless nights, between diaper changes, while soothing tears and dodging projectile vomiting, I had fallen hopelessly in love with this little girl. At that moment, I became “daddy” — and to the most wonderful girl who has ever been or ever will be, no less.
Since then, our bond has only grown. I find myself rushing home from work with barely contained excitement at getting to see and play with her. The best part of my day is when she hugs and kisses me when we put her to bed. The second best part of my day is when she greets me coming in the door from work with her hands in the air like she is signaling a touchdown, screaming “Daddy’s home!” When she refers to herself as “Daddy’s baby girl” I am filled with joy and pride. When she leans against or rests her head on me while watching Daniel Tiger, my seconds stretch to infinity; in those moments, all is right with the world and I am calm.
Katherine nurtures me. When she eats, she takes a bite, then offers one to daddy, feeding it to me by hand. Katherine offers me blankets and her beloved stuffed bunny named Bibi to hold (she has a many stuffed bunnies, all of whom are named Bibi: Bibi; Other Bibi; New Bibi; Itty Bibi; Other New Bibi; and Other Itty Bibi).
Katherine takes comfort from me when upset, frustrated or hurt, and listens to me when I tell her she needs to do something. But Katherine also orders me around like a trained pet. “Daddy fix it!” “Daddy get wawa!” “Daddy throw ‘way lady bug!” (she has taken an aversion to the lady bugs that occupy our house and thinks I throw them away in the trash). And, most often, “Daddy sit!” (pronounced in an exaggerated southern drawl as a two-syllable word, “see-it”) followed by her pointing to some location where I am supposed to do so. On “Daddy days” (when mommy sleeps in and daddy takes the helm for the morning), she likes to comb my hair and put bows in it, she tells me what she wants to wear (usually something Glenda has told her I would like) and tells me which items of my own outfit need to be changed.
My days are filled with tea parties with that warren of stuffed Bibis and a baby doll named “Baby Blue Eyes.” I am a jungle gym. We play hide and seek and peek-a-boo. She hides her toys then asks me where they are with an exaggerated hand gesture, palms up and shoulders shrugged, followed by us looking frantically in places they obviously cannot be, acting mystified that they are not there. She wants me to chase her (crawling, not walking) and lift her up when I catch her (preferably upside down), over and over, cackling with laughter the whole time, until I give out (I need to do more cardio and curls — and by “more” I mean “any at all”). I am audience to her first choir performances.
And my days are filled with dance. I hold her hands for the support she cannot give herself, and then she crouches and stands, crouches and stands, her head bobbing up and down. Sometimes it is to music we both can hear. Sometimes it is to music only she hears. These are bursts of pure joy, accompanied, music or no music, by her laughter. And always it comes with screams of “Dance! Dance!” and, of course, orders of “Daddy Dance!”
My wife has often commented that she never remembers me laughing like I do with Katherine. I didn’t. Katherine brings out laughter that I have never had. Not chuckles, but raise-the-roof, tears-in-your-eyes belly laughs — an echo of the laugh I first heard from her that day at the changing table.
Daddy is Katherine’s comforting plaything. I am her biggest Bibi. I am nurtured and loved, just as I nurture and love her in return. My love for Katherine is different than any I have felt before or knew existed. It is unconditional and boundless, life-affirming and life-changing.
I barely remember my life before Katherine and cannot imagine my life without her.
Then I got the call that told me I had no choice but to start imagining it; the physicians told me that Katherine was going to die. This was likely to occur within two to eight years. Worse yet, before the end, we would lose everything that makes Katherine “Katherine.” Each of the disorders she was likely to have was progressive. Each would rob her of her ability to speak or move long before taking away her intelligence. As I hung up the phone and went inside to tell all of this to my wife, my mind reeled with horrifying thoughts: Some day – it seemed soon — I would come home from work and she would be unable to raise her hands in that “touchdown” greeting; soon after, she would no longer be able to shout “Daddy’s home!;” no more crawling on me like a jungle gym; no more crawling away from me in chase; no more feeding me her food; no more eating it herself; no more peek-a-boo, or hide and seek; no more ordering me to “sit!;” no more night-night hugs or kisses; no more laughter;
And…no more dancing.
In a prior post, my wife told you that she did not express all of her fears to me in the months leading up to Katherine’s MRI. If this was to protect me from fear, it did not work. I had plenty of fear. I knew something was wrong. I saw a tremor in Katherine that no one else seemed to see or else dismissed. I saw the plateau in her development. I saw the lack of balance.
My Google searches between Katherine’s first birthday and her MRI appointment a month and a half after her second were filled with things like “causes of ataxia and intention tremor in an infant;” “hypotonia;” “symptoms and causes of cerebral palsy;” “genetic causes of developmental delay;” etc.; and etc. I furtively searched the Internet, like a husband hiding something racy, but this was much worse. I was hiding my fear that Katherine had a serious medical issue. I hid it to shield Glenda from unnecessary worry, although – maybe because — I knew she already carried worries of her own.
Don’t get either of us wrong. We spoke of our concerns and fears. We just did not voice their full extent, if we even comprehended them ourselves.
By the time we went for that MRI, I had convinced myself that Katherine had cerebral palsy. If so, the underlying brain injury would not be progressive. With PT and OT, I hoped she would one day be able to “re-wire” her brain so she could walk…and dance.
During part of the MRI process, my wife was allowed to stay with Katherine, while I was kicked out to the waiting area by the doctors (only one parent is allowed to accompany a child). I wandered aimlessly, until I saw a little chapel. I have always found such places peaceful, so I went inside. I glanced at a prayer book and read a couple of the fear-filled prayers of other families. This was a children’s hospital, so they were all from other parents about their own “Katherines.” Many were facing far worse than the cerebral palsy I was sure Katherine had … maybe had … feared she did not have … please, let her have. My mind went to my year of late-night “Googling” fatal conditions. I wrote in the prayer book “Please take care of Katherine. She is EVERYTHING.” I turned to walk out, but couldn’t. My hands started to shake. I had to sit down, but the pews were too far. I sat on the floor, my back against the wall and cried unsustainable, hysterical sobs. Cries I did not know I had in me until exactly that moment. Tears I had never before cried.
Then I said something that I had never consciously thought, “please let me dance at Katherine’s wedding.”
I calmed myself, dried my tears, and walked into the waiting area, just as Glenda was walking into it, too. I spent the rest of the day trying to comfort and reassure her, until I got the horrible call and had to cause Glenda more grief than most people can imagine. “Glenda, she is not alright, they say she is going to die.” I then spent the rest of the night and many days since trying to console an inconsolable, grieving mother, while finding a way to get through my own days, working, playing with Katherine, breathing, eating, and trying to maintain my own weakening grip on sanity.
Katherine’s continuing laughter has made these things possible.
That first time I asked to “dance at Katherine’s wedding,” the thought seemed simple. I wanted Katherine to be on her feet, able to walk and to dance.
In the days since, I have uttered these words many more times. Usually, I do so when I am on my knees, again crying unsustainable, hysterical sobs. Other times it is just a whispered incantation, my mantra.
It now means something different than it did that day. It is not that I want Katherine to be able to walk and to do so easily enough that she can dance. I do want these things, but my perspective has evolved. I no longer need these things.
It now means that Katherine is alive. It means that she is happy. It means that she has found love. It means that she still has those things that make her so special. It means I am blessing her union with a person who sees them, too. It means that she has someone to love her after I am gone. It means that the proper order has been restored to the universe; one where my sweet, smart and beautiful child lives on after me.
And that dance? I no longer care what form it takes. I do not care if she is dancing on her feet, or in a wheelchair. I don’t care if it is a head bob. I just want to see her happy on her wedding day, squealing “Dance! Dance!” and ordering “Daddy dance” one last time before someone else takes her hands.
Katherine, my dear baby girl, I will hold your hands, support and dance with you all the days of our lives together. But, please, please, baby girl, let me dance with you at your wedding.