I can't believe it has been almost 2 months since Rare Disease Day, and I really can't believe how much has changed in just that short amount of time. About a month ago, I was checking my weekly notifications from PubMed. I have alerts set up for keywords relating to Curren's disorder, and on this particular day, something very exciting that never had happened before happened. There was an alert for a medical publication using the keyword "HIVEP2". My heart actually stopped beating for a few seconds as read the name of the paper, "Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features". Were there other children that had been found? Is there active research going on? I quickly scanned the document and found three incredible and somewhat unbelievable things:
Our advocacy journey has catapulted from next to nothing, to phenomenal (given the context). I was able to contact and discuss Curren's case with Dr Wendy Chung, the senior author from Columbia. We were also accepted into a study called the Simons VIP (Variation in Individuals Project), that aims to collect natural history information for families with specific genetic changes that have a known association to neurodevelopmental disorders, like seizures, developmental delay, and/or features of autism. We are hoping to get enough families enrolled in the study to begin lab studies specific to how HIVEP2 works. Curren has also just been accepted into another study through the University of Groningen in the Netherlands. The project is working to gather information from parents to better understand chromosome 6 abnormalities, including gene mutations. We also found out that a 10th child was diagnosed with HIVEP2 dysfunction last week (this is outside of the 9 published children). We have also had some incredible support from the local community. The Cove Merchant's Association is hosting the annual Port Canaveral Mac Attack fishing tournament on Saturday June 18th, and they have decided to donate tournament proceeds to Ability Plus in Melbourne to sponsor an intensive therapy program for Curren and to help other children in need. Also, Curren has created some bright and beautiful artwork, and my wonderful friend Amy has designed special Jamberry nail wraps from his work! Our friend Ryann also has a beautiful and fun bubble design. These two special edition Jamberry nail wrap collections are bold and perfect for summer, and proceeds benefit HIVEP2 support. We also recently attended a wonderful event, hosted by Ability Plus and No Limits Academy - the Everyone Can Dance Ball. The resources that these organizations provide to the community are incredible, and we are so blessed to be part of their village. All of Curren's therapists danced with him and everyone had a blast. Here are some of my favorite pictures, wasn't he so dapper? I had no idea that we would come so far in such a short period of time, and it's hard to imagine what the next few months may have in store. I am so grateful to everyone that is rooting for Curren and keeping us in your thoughts and prayers!
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The Rare Disease Day 2016 slogan ‘Join us in making the voice of rare diseases heard’ is a charge for everyone to join the rare disease community in making known the impact of rare diseases. I am happy to share Curren's story, in the hopes that his voice helps to bring about change! Curren’s first few weeks of life started out calm and beautiful. But he caught his first cold when he was 6 weeks old, and was perpetually sick for the next year and a half. We went to the ER at 4 months old due to respiratory distress. Shortly after, Curren was diagnosed with failure to thrive due to weight loss. Over the next few years, Curren’s growth and development remained stagnant as we desperately tried to pinpoint the reason behind his delays and regressions. We experienced incredible highs and heart-breaking lows, but mostly we felt isolated and alone. Eventually we arrived at an answer. Curren has a single-point mutation in the HIVEP2 gene that is predicted to affect brain growth and development, immunity, hormone production, and bone remodeling. There is one other child in the US currently known to have a HIVEP2 loss-of-function mutation - our friend Ryann. Because our voice is so small, we have not found much in the way of understanding our diagnosis, or possible treatment/management options. We have no information about prognosis. The response from most doctors or programs is one of two: (1) You already have a diagnosis, we are here to help the undiagnosed, or (2) There is nothing more you can be doing to help your child. I can't accept the second response.
I have been doing research on the HIVPE2 gene function, and have found affected pathways that are also compromised in more well-researched syndromes that currently have treatment trials underway (Phelan-McDermid Syndrome SHANK mutations and HIVEP2 both affect SSTR-2 function, Rett Syndrome gene mutations and HIVEP2 both upregulate the NF-kB pathway, increased MGluR5 signaling is common to both Fragile X and HIVEP2). My biggest hope for the future is that a more comprehensive approach can be taken with rare diseases. What if one of the treatments for a more well-known disease could benefit Curren and Ryann (and possibly many others)? I spoke with the doctor overseeing the Phelan-McDermid and Autism Specrum Disorder IGF-1 clinical trials regarding the common pathways I had found, and if he thought that IGF-1 treatments might benefit Curren. The response was that it was likely, but we don't meet the criteria for any of the trials, and the IGF-1 treatments currently cost over $100,000 a year. I am in awe of the advancements in the field of clinical and scientific research, but I wish there was a quicker way to apply broad findings to specific cases. It is heartbreaking to see Curren break down in frustration due to his current limitations with communication and mobility. I want so badly to give him every opportunity to be able to express himself and move independently. My mission is to keep my son happy and healthy, and I believe that will be best achieved through accelerating research and raising awareness. My hope is that World Rare Disease Day brings a new level of awareness to a critical issue. More people are affected by Rare Diseases than cancer and AIDS combined, but many with Rare Diseases have no resources, support groups, or research opportunities. Please help Curren's and Ryann's (and all the beautiful others) voice be heard by sharing our story! It's hard to believe that it is now 2016. What a whirlwind of craziness 2015 was, and it has come and gone. Personally, I was not a fan. I mean it was hard to beat 2014 - new fantastic house, new adorable baby, 12 week maternity leave to hang with my kiddos - but 2015 wasn't even in the running. I feel like we were pretty much stuck under a dark stormy cloud the.entire.year. I am so looking forward to a better 2016, and we're starting off with a bang! Tomorrow we leave for our first big medical adventure up north. We will be seeing several of the doctors that contributed to a recent HIVEP2 medical publication at Kennedy Krieger. We will also be meeting with the director of clinical genetics at the Children's Hospital of Philadelphia. I am super excited (and nervous) about the trip, and really hoping to get some better insight into Curren's care and treatment. I'm also hoping that Curren doesn't get sick from the planes and hospitals, that we don't freeze to death (the low is 16!), and that I can accommodate Curren's gluten-free/dairy-free diet while we travel. I also wanted to share a great book I started reading over the holiday, and I think it would appeal to all walks of life. "Far from the Tree" by Andrew Solomon is about ordinary people facing extreme, and potentially isolating, challenges. The book focuses on the search for identity through struggle. I underlined a short passage, and I'm going to make it my thesis for 2016: Life is enriched by difficulty; love is made more acute when it requires exertion.....It is not suffering that is precious, but the concentric pearlescence with which we contain it. The raw grit of anguish will never be in short supply. There is enough of it in the happiest life to serve these instructive purposes and there always will be....We all have our darkness, and the trick is making something exalted of it. I hope that everyone can make the most of their darkness, and have a wonderful new year. Here's to 2016! A lot has happened in the past week or so. First, I can't even begin to explain the overwhelming support that my family has felt since we received the news of Curren's rare genetic syndrome a few weeks back. There are so many awesome people in this world, so thank you to all from the very bottom of my (exhausted) heart! There have been many ups and downs this week, and I want to share with everyone the good, the bad, and the ugly (but especially the good)....
The incredible news is that we have been able to make an appointment at Kennedy Krieger in the Neurogenetic Clinic to see two of the doctors that contributed to the recent medical publication on HIVEP2 mutations. There is a fabulous person that helped us get our foot in the door, and lots of recommendations from people to start there. We are beyond excited to talk to doctors that are familiar with researching HIVEP2 mutations. We are also trying to set up appointments at Johns Hopkins that would coincide with our visit to Baltimore. Fingers crossed.... On the topic of good news - here's a bunch more. Curren had his 6 month re-evaluation this week with Early Steps and he is going to be authorized for an additional session of speech therapy and occupational therapy a week. We are really looking forward to the extra help! Curren also had an appointment this past week to have new orthotic braces made, which is fabulous news because it means his feet are finally growing. We were also assigned a case manager through our insurance company this past week. She seems super fabulous, and I think she will be a great asset to us - as we very frequently have claims denied, and some of Curren's very best therapists and specialists are out of network and currently not covered by insurance. And we also had a initial appointment with the Scott Center for Autism this week. We're hoping that the behavioral therapy they offer will become available to Curren to help with some of his frustrations. So, on to the not so good - we got a call from the preschool the other week that they were afraid Curren was having a seizure. He was playing in the gym and just fell over. His body went completely limp and he had a staring spell for a few minutes where he wasn't able to focus or look at anyone. On our pediatrician's recommendation, we took Curren to the local ER, where we had some really good, and some really not so good experiences. What we found out was that Curren's blood sugar was at 40 when we arrived. He also had very low CO2 levels, and was diagnosed with acidosis (his metabolic pH level was more acidic than it should have been). They had an awful time getting an IV in his body, and from this point began blood sugar monitoring every 1-2 hours (which was also awful, but necessary). Curren did magnificent in his CAT scan, he laid completely still as a statue, and the results of the scan were normal. The local hospital got in touch with our Neurologist at Nemours, and the verdict was that we needed to be there. Curren was transported by ambulance to Nemours, so that he could be in the best hands at the children's hospital. It was great that we were in such good hands. What wasn't great was the fact that people kept coming in to our room every 30 minutes or so, usually to poke Curren. And when there weren't people in the room, his alarms were going off every couple minutes or so. I don't think either one of us got more than 15 consecutive minutes of sleep through the night. Curren began an EEG in the morning, to see if any more seizure activity could be recorded. His CO2 and blood sugar slowly stabilized throughout the day, and we saw no seizures. There was, however, a new area of his brain that showed seizure-like activity - this time it was his left temporal area (in addition to his left occipital area). At the end of the day, everyone decided that all the numbers were stable enough and we could go home. This was fabulous news, considering Curren was basically miserable in the hospital - between all the wires and the constant pokes, he was completely skeptical of everything and everyone in the hospital. So on to more good news - we followed up with our pediatrician after the hospital stay and Curren's blood sugar was perfect. We don't really know if a seizure triggered low CO2/acidosis/low blood sugar, or if low blood sugar triggered a seizure. But either way, things have been much better since the hospital. We have been feeding this guys every 1-2 hours to be on the safe side, and things have been great. Aside from the hospital encounter, it hasn't been the most wonderful of times. I am still trying to wrap my head around the genetic diagnosis we received a few weeks ago. I have been googling my brain out, and reading some scary things. I wish that life could go on hold for a few hours (or just maybe a couple minutes?) so I could get a chance to catch my breath and focus, but there is a 2 year old and a 6 year old, and a +full time job, and laundry, and a gluten-free/dairy-free diet prep for the week, and homework. I don't know what the future will hold. Will my littlest require 24-hour care for the remainder of his life? Based on the information I have today, it's probable. Do his genetic condition predispose him to some nasties? Seemingly so. But I have a fabulous smiling face, and that's truly all I need. I will go to the ends of the earth to find options to allow him to be his personal best. And that's the next chapter... This past week, we received information about Curren that is both hopeful and heartbreaking at the same time. My very first post touched on my anxiety over the unknown, and with this information now comes a whole new level of anxiety. Curren’s Whole Exome Sequencing genetic testing results came in, after over 4 months of (very anxiously) waiting. The test was denied by insurance, on the premise that it wasn’t medically necessary. Whole Exome Sequencing typically has about a 25% chance of providing meaningful results, and in our case, we were told it would be closer to 35%, due Curren’s severe developmental delays. Since the coverage was denied by insurance, I didn’t expect to get the results. And even if it were to be analyzed, the odds were greater than not of getting useful information back….and yet somehow we did.
We found out that Curren has a variant (D397Y) in his HIVEP2 gene that is most likely causing severe developmental delays and chronic medical problems. It is incredibly rare – according to GeneDx there are only 3 others in the world that are currently known to have a HIVEP2 variant, and each of these individuals have unique variants. The clinical features of HIVEP2 mutations are moderate to severe intellectual disability, developmental delay, autism spectrum disorder, easy fatigability, and hypotonia (low muscle tone). The HIVEP2 gene's function is very complex - it is responsible for regulating the activity of about 25 different genes that control brain growth and development. My son’s variant is predicted to be damaging to DNA structure and function, resulting in loss of function in the brain. Other functions that seem to be affected are cell immunity, brain signaling pathways, pituitary hormone production, bone remodeling, and memory. All of this from one misspelling in a series of 2446 amino acids, in one gene of over 20,000. It is just a tiny mistake in the grand context of things, but so significant to the overall function of the brain. There have been recent lab studies on mice where the HIVEP2 gene has been made inoperative, and the results were brain inflammation, memory deficits, and hyperactivity. The mice were treated with anti-inflammatories and other trial medications and some of their neurological features improved. I have hope that therapeutic options like these may eventually become available for Curren. Curren is now two years old, and has many severe deficits. He is not able to yet crawl, speak words, or communicate through signing, gestures, or pointing. He has been sick for more of his life than not - I tallied up the courses of antibiotics he has been on, and it has been 17 times in 25 months of life. He is in the 1st percentile for height, 3rd percentile for weight, and 7th percentile for head circumference, despite a modified high-calorie/high-fat/high-protein diet. He is in 8 hours of therapy weekly, attends an early intervention preschool part-time, and his daddy now stays home with him to do lots of one-on-one work and bring him to all his appointments. Above all else, my most important job in life right now is to be Curren’s voice. I want the world to know just how important my son’s development is. It is heartbreaking to see him master a simple skill (like waving a month ago) and then lose it. As incredible as it was that he crawled on his hands and knees with assistance a few weeks ago (accomplishments!), he has not been able to do it again since. My hope is that our therapeutic options don't end here. With the new information we now have, I want my son to have the opportunity to see doctors and researchers that have an interest in pursuing management and treatment options tailored to his unique challenges. I know that there are (incredibly smart) people in this world that would be very interested in researching this further, we just need to find them! If you are reading this post, could you please help Curren and share this information with the world? My biggest hope right now is that his information will somehow fall into the hands of the right person. We are willing to travel anywhere to find someone interested in helping my son overcome/manage his biological barriers. Thank you all so much from the very bottom of my heart. |
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About MeI am a mother, architect, wife, and a lover (not a fighter) - with a thirst for knowledge. My journey been recently refocused, as my family navigates through the world of medical and developmental uncertainty in hopes of providing every opportunity for my son to be his personal best in life. Categories
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