Dr. Rowena Ng, Ph.D is looking for participants for a new research study.
Dr. Ng’s research team is completing a retrospective study that involves reviewing participants’ past neuropsychological or psychological evaluations to determine the cognitive developmental pattern associated with KAT6B disorders. Currently, this area is not well published, and therefore determining appropriate early treatments can be challenging. These results will allow us to better understand the specific cognitive strengths/weaknesses seen among this syndrome and the differences found with the different gene variants, which in turn can inform more targeted interventions in early childhood.
If you are interested, please email Dr. Ng and she will follow-up with you with further instructions. This will largely involve you sending any of your child’s previously completed neuropsychological or psychological evaluation reports so they can compile cognitive data across those affected by KAT6B mutation. Dr. Ng is happy to answer any questions you may have.
The 4th International KAT6A and KAT6B Conference aims to support individuals and their families living with KAT6A and KAT6B syndromes. With the goal to solidify KAT6A and KAT6B research internationally, this conference will also enable an open dialogue between families, clinicians and researchers.
TARGETED PARTICIPANTS
Parents, caregivers, health care professionals, clinicians and researchers who are concerned with the care of children with KAT6 syndromes.
WHAT’S IN THIS YEAR’S CONFERENCE?
– Presentations by experts in KAT6A and KAT6B research fields
– Opportunities to enroll in research studies on KAT6A and KAT6B gene variations
– Networking with the KAT6 Foundation
– Personal connections with KAT6 families, researchers and therapists
– Appointments with clinical geneticists, pediatric neurologists, and other health care professionals
The Serrano Lab and the KAT6 Foundation organized a satellite event to share how we research rare disorders and for you to have a tour of the Lab.
What happens after we draw blood from patients?
What is an induced Pluripotent Stem Cell (iPSC)?
How do researchers work with them?
How does that benefit our community?
This event is free and everyone is welcomed to attend.
KAT6A and KAT6B patient-derived induced Pluripotent Stem Cell (iPSC) Bank
The Serrano Lab at the Center for Regenerative Medicine (CReM) is working together with the KAT6 Foundation to establish the first KAT6A and KAT6B patient-derived iPSC bank. The CReM bank will serve as a repository for sharing KAT6A and KAT6B human iPSC lines with internal and external investigators to conduct both basic and translational research.
If the KAT6A or KAT6B patient is unable to attend the conference. You can transport their sample by following theseinstructions.
Genomic Evaluation of Rare Diseases
UCLA researchers are seeking individuals with rare genetic disorders and their family members to participate in a research study funded by the National Institutes of Health (NIH) & California Institute for Regenerative Medicine (CIRM).
We want to draw blood for laboratory studies of cells. We will use blood samples to identify disease-associated biomarkers for diagnosis and for future assessment of any new therapies. We will draw 3 vials of blood for this study. All ages may participate. We encourage parents and siblings to participate as controls samples for this study.
This research study aims to identify the unique cognitive profile of KAT6B disorders. Participants will be given a battery of cognitive tests (e.g., paper and pencil or computerized puzzles and games) that will take about 90 minutes to complete. Please note, study enrollment and scheduling for this study at the conference are based on a first come first serve basis.
Dr. Dettin will summarize her publication methods and results of the study for the KAT6 Community.
About the speaker:
Monica Dettin is Assistant Professor of Organic Chemistry at the Department of Industrial Engineering, University of Padova, Italy. Her research interests are focused on the following areas: synthesis and characterization of biologically active biopolymers; studies on structure-activity relationship in biopolymers; conformational and structural studies; maturation process of pro-proteins; interaction between biomaterials and biological tissues; peptide mimicry of adhesive proteins and growth factors; scaffolds of self-assembling peptides; chemoselective ligation.
To participate in this event, please obtain the Zoom link in the KAT6A support group on Facebook, or email support@kat6a.org.
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We are proud to report that research led by Dr. José A. Sánchez-Alcázar and his team was published by Genes on November 15, 2022 in an article titled Pantothenate and L-carnitine Supplementation Corrects Pathological Alterations in Cellular Models of KAT6A Syndrome. This is an important milestone for our Foundation as it is the first research project that we directly funded to reach publication, and is an important step forward on the path to finding a treatment for KAT6 individuals. Development of surrogate models simulating KAT6A gene variation is the first step towards understanding the pathophysiological alterations caused by this gene variation. By outlining pathophysiological pathways, treatment model(s) addressing alterations in these pathways can be developed for testing.
Three individuals with KAT6A gene variation participated in the study conducted at Universidad Pablo de Olavide in Spain. An initial series of experiments generated evidence supporting the use of patient-derived fibroblast to study KAT6A gene variation. The team identified four critical pathophysiological processes altered by KAT6A gene variation: 1) Coenzyme A (CoA) metabolism, 2) Iron metabolism, 3) Enzymatic antioxidant system and 4) Mitochondrial function. Two compounds were identified to have a positive impact on the altered physiological pathways. These compounds are: 1) Pantothenate and 2) L-carnitine. Pantothenate is a CoA metabolism activator and L-carnitine is a mitochondrial boosting agent. Supplementation with pantothenate and L-carnitine supported the survival of the KAT6A fibroblast in a stress inducing medium. The concentration of pantothenate and L-carnitine varied in all three KAT6A cell lines suggesting that different type of mutations respond differently to these positive compounds. The KAT6A gene plays a significant role in histone acetylation which is a key process involved in cell progression and differentiation. Supplementation with pantothenate and L-carnitine resulted in significant increase in histone acetylation, recovery of gene expression patterns and expression levels of proteins affected due to the KAT6A gene variation.
We want to extend our sincere thanks to Dr. José A. Sánchez-Alcázar and his entire team for their professionalism and commitment to rare disease research and the KAT6 community. We look forward to building upon this partnership in the future.
Parents and caregivers of children or adults with KAT6 disorders are the first to recognize whether the person they care for is in distress. Those continually looking after the person’s needs are the best ones to intervene and advocate for medical care when it appears that a problem is present and getting worse. But what are we looking for and when might it call for emergency care?
INTESTINAL BLOCKAGE
Gastrointestinal issues are common with KAT6 disorders. Low muscle tone throughout the body may mean low motility in the gut — weak contraction of the muscles that mix and propel contents in the gastrointestinal tract. When there is a temporary lack of normal muscle contractions of the intestines this is known as ileus — not a blockage, but a stoppage. (Think of a blockage as a train wreck, preventing any other train from passing through, and think of a stoppage as merely a train sitting on the tracks and failing to move along.)
When the contents of the upper or lower bowel cease to move, the resulting mass can become enlarged and can harden as it dries out, stretching the part of the intestine where the mass occurs. Regular contractions can return and eventually move it along, but if the contents sit too long they can begin to ferment and decay, with potentially serious results. Vomiting and diarrhea, for example, are normal consequences once the body applies its other resources to the obstruction.
If it does not eventually start moving on its own it may respond to non-invasive treatments such as stimulants taken orally or a rectal enema, depending on proper assessment of the location of the problem. But if there is a physical barrier to continued movement of intestinal contents, the problem can quickly become life-threatening.
MALROTATION AND VOLVULUS
Around the tenth week of gestation, as the intestinal tract is developing, it normally moves from the base of the umbilical cord into the abdominal cavity. As the intestine descends into the abdomen, it makes two rotations and settles into its normal position. When a portion of the intestine, or even the entire intestinal tract, fails to lie properly in this space, it ls known as a malrotation.
A malrotation may cause immediate symptoms and problems after a baby is born or may lead only to intermittent trouble, or it may cause no problems at all. In some people it is not discovered until well into adulthood or perhaps never discovered at all. In others, it can be the source of repeated obstructions. The point is, a malrotation is an anatomical defect and one that must be suspected if problems arise, especially in early childhood. It can lead either to continuous or intermittent problems but is not necessarily dangerous.
When a loop of intestine and the membrane that holds it in place twist around each other like sausage links or a kinked garden hose, this causes a bowel obstruction called a volvulus. A certain kind of volvulus in a horse is commonly called a torsion. It is not going to clear and open back up on its own, and normal muscle contractions in the gut are not going to force a trapped mass of intestinal contents to move past it.
The trapped material, already partially digested, continues to break down, though, and some contents may be ejected as diarrhea or gas, while most of it will remain and swell the gut. A person suffering a volvulus, who enters emergency surgery soon enough, may still lose part of the intestinal tract in surgery. Without emergency surgery a volvulus is almost certain to be fatal.
If a volvulus is suspected in an emergency room, a buildup of gas in the intestine may show up on a series of x-rays, which must be taken at intervals long enough for changes to appear but no so long that surgery comes too late.
OTHER GI ISSUES
The esophageal sphincter is the valve between the esophagus and the stomach. When the muscle that keeps this valve closed is weak, a blast of burning stomach acid may rise as far as the throat. This is acid reflux. A baby with KAT6A or KAT6B can be resting quietly in a baby seat, alert and cheerful, and suddenly scream in pain and terror. If this happens with any frequency, reflux should be suspected when nothing else is likely.
Dumping syndrome is a group of symptoms, such as diarrhea, nausea, and feeling light-headed or tired after a meal, that are caused by rapid gastric emptying, a condition in which food moves too quickly from the stomach to the duodenum. This can become an issue after a person has undergone GI surgery. Adjustments in diet or medicine can resolve things, and, if surgery was involved, time may be the best healer.
OUR NEED TO REMAIN VIGILANT
Communication problems are common with the KAT6 population as well as an apparent high tolerance for pain. Children and adults with KAT6 disorders, especially those who can’t tell us that something hurts or where it hurts, need to be monitored continually for lack of gut movement. Constipation, (a general term for any disruption of intestinal activity that leads to pain and irregularity of bowel movements), can make a normally cheerful person irritable.
A volvulus is a rare occurrence in the general population, but among the KAT6 population it seems common enough to be of serious concern. Although we are still studying the matter and don’t have statistics, it appears that untreated bowel obstructions are the leading cause of death among children affected by KAT6 disorders.
Many of those with KAT6 disorders are tube-fed through a gastrostomy. For some, this is their only source of nutrition, and so variations in gastrointestinal activity are less likely to be caused by daily changes in diet.
What is the person’s normal frequency of bowel movements? Has it been a day longer than normal? Two days? Is she also becoming irritable, combative, unable to sleep? Does this happen in repeating cycles? What does her blood work show? What does a gastroenterologist say? Do cycles of irritability correlate with cycles of unusual toilet contents? Someone close to the patient needs to be asking these questions and insisting on answers.
People with KAT6 disorders may show no signs of a bowel obstruction until it has progressed to a serious degree. They may quietly tolerate the increasing pain until it has become severe. An obstruction can go from bad to dangerous quickly. It is hard to differentiate an obstruction from other gastro-intestinal issues. Obstructions can happen again and again and can strike at any age.
While it is probably more likely to become an issue early in a child’s life, an affected person who has a KAT6 disorder can seem to be OK for years, perhaps irritable at times for no apparent reason. Just because it hasn’t been diagnosed at an early age it could be that a complete obstruction simply hasn’t happened yet. The best prevention of complications is be on top of it all of the time. Not all doctors understand that, with a bowel blockage, you can still pass diarrhea — the assumption seems to be that if they’re passing anything at all then there’s no obstruction.
Medical services vary from country to country, and while another country may have excellent hospitals and perfectly competent doctors, they may also have different approaches to parent involvement, different protocols for intervention, and different standards for what can and should be treated.
Compounding the danger, a doctor may not consider an intestinal obstruction if a parent or caregiver hasn’t suggested it, and so a doctor wants to ascribe a change in behavior to anxiety, a virus, a food allergy, and so on. Meanwhile the child has mere hours to get the problem resolved or else irreversible damage has been done with a high potential for fatal results.
LIVING WITH IT
We aren’t supposed to tell people about our poop or ask others about theirs. With KAT6 in a family we could save a life if we get beyond that taboo. In our own experience, Beth and I share in all phases of the care of our son, Sam, who is now 32 years old. He is one of the more severely disabled individuals with KAT6A syndrome, and so we must pay constant attention to all the signs he gives us. We “read” his behavior, we both examine his bowel movements daily or at least describe to each other what he has done. (He even has an “I POOPED TODAY” T-shirt.)
Sam has had a gastrostomy and feeding tube since he was a baby and receives all medicine and sustenance through the tube. He had a nissen fundoplication during his first surgery as a baby, so he cannot burp or vomit. He had a malrotation of the duodenum at birth (corrected by surgery), reflux as a baby, a volvulus before he was two (indicated by changes in a gas pocket on successive x-rays), a second near-fatal obstruction due to adhesions, and numerous instances of ileus and other partial obstructions requiring hospital stays. As an adult he is now treated for ulcerative colitis. He does not walk and can’t speak. But he is engaging and even mischievous, affectionate, enthusiastic, and popular. When he hurts, his only ways to show it are in withdrawal, resistance, and restlessness.
We are fortunate that Sam has had doctors who care about him as a person and who listen to us, his parents. His doctors, though, need to trust what we are telling them, and so our information must be reliable. By educating ourselves, paying close attention to the signs that Sam gives us, and making sure we communicate consistently and accurately with medical providers, we have been Sam’s best advocates.
Many parents have observed GI benefits from a mitochondrial cocktail and other supplements, such as Cytra-3.Learn more about these supplements by watching Dr. Richard Kelley’s presentation from our 2022 Conference. It is essential to consult your child’s physician before starting anything new.
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The Gastrointestinal Health and Beyond in Children with Rare Genetic Variations was a 2-hour long, patient-centered, collaborative event organized by the KAT6 Foundation. It was designed to fuel conversation about the gastrointestinal challenges faced by children with KAT6A and KAT6B gene variations and enable open dialogue between families, clinicians, and researchers. The webinar provided a platform for the KAT6 community to expand its network and build connections with new researchers and experts working on tackling GI and GI related issues. More than 90 individuals registered for this event. On the day of the webinar, 20 families and 35 scientists attended the event. With some international representation, the majority of the families and researchers were based in the USA.
Dr. Tanya Tripathi, research coordinator of the KAT6 Foundation moderated three scientific presentations by renowned scientists – Dr. Sarkis Mazmanian, Dr. Gustavo Mostoslavsky and Dr. Richard I Kelley. Please read the summary of the presentations here.
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It was just a few days before Anna’s birthday and, after being in several different hospitals, we were about to receive the long-awaited answer. It didn’t seem true that we could name Anna’s problems after years of research.
What we did not expect was to be confronted with a rare genetic disease: the KAT6A syndrome. She was the 86th person in the world with that genetic variant. Our world suddenly fell silent, hearts stopped and everything went black. Bitter and sad tears, but Anna tried to comfort us by telling us that she had not cried. The doctors explained what they knew, provided support also why there is no cure or acceptable case history.
An uphill and uncertain path awaited us on the horizon. In the huge list of things to do we did a Google search: we found an in-depth description of Anna’s KAT6A syndrome! Thanks also to @pietrodurando’s suggestion, we also found the “KAT6 foundation” an American foundation that helps people and families of those living with KAT6 disorders. With a click we went from being alone to finding ourselves in a community with our same goals: the search for a cure and the improvement of the living conditions of our children, brothers and sisters!
by Alfredo Cabutto
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Our journey to diagnosis looks different than most, our journey to our boy also looks different. In the fall of 2019, my husband and I, had 3 small children and decided to take steps forward toward becoming foster parents. By springtime of 2020, we were ready to start our foster parenting classes, but the pandemic suspended in person classes. Eventually we ended up in the first zoom foster parenting classes the state of Missouri ever had. We had extra time in our licensing process, so we took the adoptive parent classes as well. Towards the end of our home study our licensing worker asked if we would consider becoming medical foster parents. Despite me telling her we had zero clue about medical children we agreed to adding medical to our license, but we never thought we would get a call for anything beyond giving simple medications!
Cut to October of 2020, on Halloween, we got a call for our first placement, a six-month-old boy was waiting in the hospital for someone to come. The first phone call didn’t provide much information, we knew he was g-tube fed, had delays, and desperately needed a safe home. We told the caseworker we didn’t know anything about tube feeding and she said we would stay over night at the hospital to train on his care. I expected my husband to say no, we already had 3 children under the age of six, this baby needed a lot of complex care, but my husband said yes and so did I.
The following day, we drove two hours to the hospital, so nervous, worrying if we could be who this boy needed. It made no sense, but it was right, a God thing. We had several phone calls with doctors and social workers between our first call and the trip to the hospital we learned the baby had a very long list of complex diagnoses. Entering his hospital room for the first time, laying eyes on him, so small, so frail, so alone was unlike anything I’ve ever experienced. My husband and I just stood there staring at him in silence, after a couple minutes my husband looked at me and said, “he’s with us now”.
We stayed three days and two nights in the hospital before bringing our boy home. During that whirlwind, we learned every aspect of his care, g-tube feeds, oxygen, suctioning, medications, physical therapies and so much more. They told us his genetic diagnosis, KAT6B mutation, no one caring for him knew what it was or what to expect long term. I googled it from the hospital room and read there were less than 100 people diagnosed worldwide. Flooded with instant panic, I stopped googling to focus on learning his day-to-day needs, until we made it home and I could do a deep dive into researching KAT6.
Our baby boy’s name was and still is Sebastian, we call him Bash for short. From the beginning his differences from typically developing babies were apparent, caused both from his genetic differences and the traumatic homelife he had lived in resulting in him coming into foster care. He was limp and stiff all at the same time. He was so underweight, failure to thrive, malnourished, dehydrated and treated for refeeding syndrome. His hair was falling out from lack of nutrition. He didn’t make eye contact; his eyes shook back and forth. He was terrified to be held, had an extreme startle response, and never relaxed in our arms. He vomited frequently. He was in survival mode just trying to recover. We had no idea what his baseline would eventually be. Slowly he began to trust us, we began to find a new normal, chaotic yet balanced routine blending our lives with his constant care and appointments. He gained weight, he began to inch alone in his physical therapy goals. We signed up for every intervention therapy we could find. The early days were so difficult and rewarding. Loving him was easy. Every day as his foster parents, we loved him as our own son, we had no idea how long he would be with us.
As the ups and downs of the foster care system played out simultaneously with the ups and downs of medical parenting, we found the KAT6 Foundation and the Facebook parent communities. We leaned into figuring out all we could to provide our boy every resource he needed. When given the opportunities he needs he happily does the work required, he is so motivated. Having a support system of other parents living this complex medical life has been invaluable. He has never stopped progressing, intensive therapy programs mixed with daily interventions from his First Steps providers has propelled him forward. We have in home nursing, along with supportive extended family and community helping to make our little world go round. He works harder than anyone I have ever known; he is such a positive light.
Being a medical foster parent is an indescribable uphill battle. Just gaining access to his complete medical records took over five months, taking my child to appointments and not knowing simple information such as birth weight or previous surgery dates was so stressful, it shouldn’t have been so hard. We spent a lot of time catching up on appointments he had missed before coming into foster care, his schedule was jam packed every day.
Grieving a diagnosis is something I know parents go through. For me, in the beginning I immediately accepted his list of known diagnoses and only grieved for the situation he had been in leading to him being taken into foster care. As the months and years have passed, he has received additional diagnoses and I have grieved them. I don’t stay down for long, his positive perspective keeps me upbeat, living five minutes at a time is how we do life now. He has a lot of accessories, a list of medical complexities and yet, is my most easy-going child. Everyone who meets him is blessed by his calm presence.
After 505 days in our home, we were able to officially adopt Bash. I was so thrilled at the courthouse when our home nurse took out her tablet and charted, “Patient was adopted today”. We celebrated him with a big party with the family and friends who have supported us on this journey. Our family truly needed him. He has made us better parents, taught our older children a lifetime of compassion and empathy, and given our family the gift of living in the present. Every family should be so blessed to have a child like him.
Kristin Ross O’Brien
Sebastian’s Mom
Boonville, Missouri
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