Just Jack: An Important Medical Update in Time for World Rare Disease Day!

WRDD19Jack is so many things. He’s capable, he cute as a button, he’s smart and he’s stubborn, he’s affectionate, he’s friendly, and he means so much to many people. But, before I even got to the chance to know and love my son, I was given a limit on his life and a limit on my time with him. With a life-limiting + incorrect diagnosis and poor prognosis, my 11-week-old was in a fight for his life. You would never believe it looking at my big healthy boy today, but he almost wasn’t here. He has a rare disease that was almost missed. Jack saw over 20 different doctors–specialties like Neurology, Human Genetics, Infectious Disease, ect.–in one of the US’ leading Children’s hospitals. Jack’s rare disorder, known as Pyridoxine Dependent Epilepsy(PDE), was overlooked for 6 solid months while he struggled and suffered with intractable seizures and a subsequent brain injury. This slow struggle towards a correct diagnosis is not uncommon in the rare disease community, and in fact, Jack was diagnosed quickly for having a rare disease. According to Global Genes (my go-to for all things rare and genetics related), the average time it takes for a rare disease patient to get a correct diagnosis is 4.8 years. My son could not have survived this long without the correct diagnosis + treatment and that is why I tell as many people as will listen. Awareness is everything in the rare disease community, especially when there is a treatment that is absolutely life saving like Triple Therapy for PDE.

I was thrilled when I was told we would be swapping out (slowly of course) 5 different AEDs (Phenobarb, Keppra, Topamax, Fospheny, AND the regular use of diazepam) for Pyridoxine (B6) and a new diet. For my non-neuro friends, I used the “pet words” for some of the AEDs (Anti-Epilepsy Drugs) because it’s one way we exert a little control over the meds. (ha!) WHAT? Is this even real? We went from absolute devastation, being told that our infant son had mitochondrial disease and his brain would “continue to atrophy until he passed away” to he has an Inborn Error of Metabolism and needs to see Genetics and a Metabolic Nutritionist ASAP. So he is going to live? YES! I learned the hardest way possible that doctors are not always right; they do not get to write the story of your child’s life and the fight is always worth it! I know many readers already know the entire story, but the Mito diagnosis was Jack’s second misdiagnosis. When he was just 10 days old and in the PICU after being life-flighted, we were told that he had a Hypoxic Ischemic Encephalopothy (HIE). There were pieces of Jack that fit with each diagnosis at the time so the neuro team did what they could with the information available at the time. However, the information could and should be better for inborn errors in metabolism (like PDE) that can be tested and added to the newborn screening process. As the mother of a kiddo with a rare disease, I can tell you caregivers fight, scrap, and claw for every inch of information that will help our children. And the battle is always worth it.

All of this being said, I have learned SO MUCH about PDE and want to give an update on Jack Jack. This has taken me so long for a few reasons: I want to thoughtfully explain PDE in a way that does the patient’s justice AND this update involves a subject that makes me most uncomfortable–intellectual disability. We have been prepared for many things with Jack; from the beginning we were prepared for a severely brain-injured child with a completely unpredictable future, next we were prepped (by doctors) for our son to die, then we were told his true diagnosis and prepared for unpredictable delays. Whew! I’m grateful for, not disheartened by, these diagnoses now because they made me fight like hell for my son. Jack is now 2.5-years-old and will be 3 in July. He has carried and still carries many of these diagnoses: PDE, ASD, Apraxia, SPD, GDD, Hypotonia, CP, etc. Last month Jack had two major appointments that really helped me understand, come to terms if you will, with what my son’s diagnosis of PDE truly means (at least for him, each child is so different). Here’s the medical portion: Jack is sometimes (hopefully not all the time) having seizures while he sleeps. His EEG tells his neurologist that is brain is processing at a little bit of a slower pace than typical kiddos while he is awake. These were both things I was unprepared to hear. Jack is currently on 300mg of Pyridoxine, which is a lot considering the main side effect is peripheral neuropathies. Most people need only 2mg of B6 per day just to put that in perspective. Jack is actually doing quite well currently and on an upswing with development so we aren’t interested in adding an AED at this time. My main question that I kept coming back to was, “will Jack have an intellectual disability?” I don’t know why I didn’t really prepare myself for this portion of Jack’s disorder; after all, it is written quite clearly that PDE patients are likely to have a learning disability. The idea of the gap between Jack and his peers widening absolutely crushes my heart, but I don’t have much time to mourn so on we go! Another interesting development in Jack’s diagnoses is that both the child psychologist and neuro-development team that Jack saw do NOT think Jack has ASD. They said that Jack has some very severe delays, most severe being his gross motor skills. They said that Jack struggles to orient himself with other people because it’s all he can do to hold himself up. He does not make good eye contact because his neck and core are so weak. He wants to make eye contact, they say, but it’s just too difficult because he is so big, yet his tone is so low. Sometimes he just looks like all his parts don’t work together quite right, but it’s what make him Jack Jack! Needless to say, these appointments have clarified and sharped so many things for me.

Jack’s incredible neurologist, Dr. Koh of Children’s Healthcare of Atlanta, told me that while many of those above diagnoses apply to Jack clinically, he doesn’t need them in addition because he has the “unifying diagnosis” of Pyridoxine Dependent Epilepsy. PDE, she explained, is a “metabolic encephalopothy”. What the hell does that mean? It means that Jack’s brain works differently at the metabolic level, causing him to develop differently than neuro-typical children. When this “metabolic encephalopthy” was not being properly treated, it caused damaged to Jack’s brain. The damage, or what they like to the “dull spot” on Jack’s MRI explains his ataxia, but PDE explains everything else. PDE is rare so there isn’t much written, not many resources to compare, and not enough kids diagnosed and treated properly to predict what Jack’s future looks like. I know all the rare patient caregivers can relate to that. Interestingly, Jack’s doctors (not just Dr. Koh) say that PDE is really the only diagnosis Jack needs because PDE implies developmental delays, epilepsy, hypotonia, etc. While I have always understood this, I have also spent so much of my time fighting with insurance for early intervention services and keeping ER doctors from killing my son because PDE isn’t an instantly recognizable diagnosis. An insurance representative once said to me, “I don’t understand why your son needs so many therapies, it’s not he has Down Syndrome or something”. I hung up immediately so my anger for my son and then my friends and loved ones with Down Syndrome didn’t vaporize him through the phone. Maybe, hopefully it still did. Dr. Koh basically told me that it’s my job to change this and make people recognize and remember PDE. So remember this: PDE is super similar to PKU and both can kill you if not properly treated.

I am always up to chat more about PDE and provide resources so don’t hesitate to reach out! Happy Rare Disease Day, my incredible friends!! ❤

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Rare isn’t all unicorns and sparkles: World Rare Disease Day 2019

IMG-9315What does World Rare Disease Day mean to you? Have you ever even heard of it? Prior to having Jack, I didn’t even know there was a day dedicated to individuals who face the unknown daily. I say the unknown because that is basically what rare means; it means you will hear a lot of “we just don’t know yet” or “we have to wait and see”. Rare looks a a bit more medical than magical in the real world. But rare is also beautiful, right? That’s what all the cute unicorn tees tell us…in a field of horses be a unicorn or whatever. Of course rare is beautiful in so many ways, but it’s also lonely. What they don’t tell you is that once you have that unicorn or are that unicorn, you will no longer have that field of horses. All of the sudden you are exposed and alone all at once. It’s almost like you don’t really exist anymore because your life is too difficult to fathom. My 2.5-year-old son is my unicorn and he is the most incredible little buddy who also happens to have a rare genetic and metabolic disorder called Pyridoxine Dependent Epilepsy (PDE).

Before Jack I had no idea there were so many genetic disorders, so many rare disorders of all varieties. I try really hard to read and learn a little about each new disorder that I learn about through a social media photo, hashtag, or a meeting at an outreach event, etc. I think that’s one the best things we can do to show respect for the brave humans who fight these disorders daily. That being said, PDE is pretty confusing to most people. I understand pretty well because I have to, but here goes:

“Pyridoxine-dependent epilepsy (PDE) is a rare genetic condition characterized by intractable and recurrent neonatal seizures that are uniquely alleviated by high doses of pyridoxine (vitamin B6). This recessive disease is caused by mutations in ALDH7A1, a gene encoding Antiquitin, an enzyme central to lysine degradation. This results in the pathogenic accumulation of the lysine intermediates Aminoadipate Semialdehyde (AASA) and its cyclic equilibrium form Piperideine-6-carboxylate (P6C) in body fluids; P6C reacts with pyridoxal-5′-phosphate (PLP, the active form of vitamin B6) causing its inactivation and leading to pyridoxine-dependent seizures. While PDE is responsive to pharmacological dosages of pyridoxine, despite lifelong supplementation, neurodevelopment delays are observed in >75% of PDE cases. Thus, adjunct treatment strategies are emerging to both improve seizure control and moderate the delays in cognition. These adjunctive therapies, lysine restriction and arginine supplementation, separately or in combination (with pyridoxine thus termed ‘triple therapy’), have shown promising results and are recommended in all PDE patients.” —> This is the treatment plan Jack is on, but because he wasn’t properly diagnosed until almost 6 months old it’s a very “wait and see” outcome for him and most patients until there is more research.

So let’s talk a little bit more about our unicorns, our rare disease warriors, and what they mean to the world. I recently worked with a media team in the UK to share Jack’s story. They made a beautiful video that had the most amazing supportive comments attached. They also published a written article about Jack. I am always asked what my goals are or plans are going forward with advocacy? The interviewer asked me this question and I answered that my first goal is to help get PDE added to the newborn screening process! Cool, right? (I think so!) But of course there were a few ignorant comments that struck me on this one. Here are two of the comments (one kinder than the other):

1.) I sympathize with the anguish these parents went through, but I’m not sure it’s practical to test every baby for something so rare.”

2.) You want every newborn tested for one of the world’s rarest diseases??

When people ask these sorts of questions or make comments like this, I get so confused. Do they know what the newborn screening process is? It already happens to every child, a little heel stick. Why is it so crazy to also test that blood for PDE bio markers? IT COULD LITERALLY SAVE LIVES! It literally makes me cringe because it seems like people don’t even know what newborn screening is or why it’s done. These are people whose future children I could be advocating for, but they don’t care enough to (at the very least) not make a comment that they don’t even understand. I guarantee if these commenters had a loved one with a rare disorder then they would care about rare, or least empathy, a bit more. Maybe the article didn’t do a good job of explaining why I want PDE added to the newborn screening process, but that was not the purpose of the article. The purpose was to celebrate a very brave little boy and shine a light on a rare disorder to give hope to others.

I did not even know that PDE could be screened for in an infant since my son went almost six months with having a correct diagnosis. During this time, he suffered immensely and even has a brain injury due to late diagnosis. Jack’s geneticist is the one who brought to light the fact that there are PDE bio markers that can be tested in newborns, just as there are bio markers that are tested in Jack every 3 months. In addition, if you take Jack’s case along with much of the research, it is quite to clear to see that many PDE patients go undiagnosed or misdiagnosed. Maybe PDE isn’t even as rare as we think. We just don’t know, which is why awareness and advocacy is important to me. I was even told by Jack’s neurologist that before the gene associated was identified, many of the kiddos with PDE passed away because they were resistant to all typical anti-epilepsy drugs (AEDs) and go into status so easily. Many PDE patients begin having seizures in-utero just as Jack did (only we didn’t know at the time) so by the time they come into the world, they have already had tons of strain on their developing brains. PDE can be most closely related with PKU, the disorder already tested for on the newborn screening because early metabolic treatment is so necessary. PKU is still considered a rare disorder even though the incidence is much higher than PDE. If the brain development and overall outcome of your child depended on as early a diagnosis as possible, then you would care about newborn screening as well.

PDE, along with PKU and many other disorders, is known as an inborn error of metabolism. Diabetes is the most common form of metabolic disorder if that helps at all. Basically people with metabolic disorders are lacking something important needed to help their bodies/brain function properly. These disorders are quite cruel, many are progressive, and even more have no treatment. This is why we should care about rare. We should care about rare not only because we love our beautiful unicorns, but also because the reality of the rare life is a desperate and isolating one. I guess a sad unicorn doesn’t make as cute of a tee, though. Care about rare because it’s all around and because it’s worth making the effort to try to understand, connect, and offer hope to others. Advocacy, awareness, inclusion, and kindness are the best way to beat the comments and ableism that make rare as lonely as it is beautiful.

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