IamA mom to a child with the ultra rare disease Hunter Syndrome trying to make a difference on World Rare Disease Day (today). AMA!

1. How did you find out?

2. What's your daily routine like?

3. Can your child stay in the program / study as infinitum?

1. I found out he had Hunter Syndrome because my mom happened to see an episode of the show Mystery Diagnosis about a boy with Hunter Syndrome. Totally miraculous. She's an RN so she realized by the end of the show that he probably had this horrible disease and had to tell me. His symptoms were so mild at the time that they wouldn't have been caught for at least a year or two, if that.
2. He goes to school pretty much like a typical kiddo and is in special education and inclusion classes. He loves school. I work with him on reading and skills after school. We do infusion once a week, usually on Sunday nights, and that lasts about 4 hours. And we have lots of doctor trips and visits for the clinical trial each month.
3. He is on the clinical trial drug (which is a spinal infusion given in the hospital each month) for free until it gets FDA approved. Then hopefully that happens and insurance will pay for it. But that's a whole new issue.

As the parent of a child with a rare disease, thanks for highlighting World Rare Disease Day!

How do you deal with teachers/caregivers/etc who either cannot or will not understand the special needs of your child? Or is this not an issue you face?

Our particular issue has no externally visible signs, so it's a constant war to keep him healthy in school.

We faced this issue more early on, when the signs and symptoms were not as obvious, as seems to be your case as well. I always tried to be prepared beforehand with what I knew I wanted and why, point by point. And then always having validation, whether it was someone that went with me to IEP meetings that was knowledgeable about my son's needs and the disease, or letters from relevant doctors about exactly what his needs were (in our case, geneticists and neuropsychologists), even if I had to draft those letters and submit them to the doctors for them to revise or just adopt, and literature. Being a lawyer always helped too, but in reality, having that "advocate" to back you up and validate what you're saying is always important.

What rare disease does your child have?

Phenylketonuria, aka PKU. An inborn inability to process the amino acid Phenylalanine, so it requires a steadfast lifetime low protein (depends on the patient, but 5g a day for us) diet and special supplements.

The work of groups like NORD and government programs like the ADA and various medical food acts are incredibly helpful for us.

Ah, I spoke alongside several PKU advocates at the Patient-Focused Drug Development meetings at FDA last year. I can possibly imagine the challenges you have based on their testimony. Have you tried showing them video of what the process is in the body and brain when the diet is not followed? Now that my son is doing fairly well, I do get the response sometimes that he just must be a "mild case" but I have to constantly confirm to people that no, X is what would absolutely happen to him without this drug and we have to make that process as seamless as possible for him to get it. Blessings to you.

Hi Melissa, thanks for doing this AMA.

I read your piece about managing expectations.

• 1. How do your other children understand their brother's condition?
• 2. How have you been able to afford a medical expense that is (annually) nearly 10 times the average US American's annual income?

1. We've always explained his condition on an age appropriate level. Our older boys are now pre-teens and have met many other children with his same condition, in various stages of the disease, and some receiving the experimental medicine and some not. Many times, he's still just the annoying little brother, which I consider a fantastic thing, but they are now realizing that his special needs are often things he can't control and that he could be doing much, much worse. It is a fine line. They have spoken maturely in recent months about appreciating how well he's doing and wishing other boys could receive the same medication and hopefully live.
2. The medication is covered by insurance except for our deductible and co-insurance. Some of that is covered by co-pay assistance programs by the pharmaceutical company. Patients and families who take these high dollar medications feel very conflicted about something that is saving the lives of people they know and love, but is so expensive. I wrote about this conflict and other thoughts in a blog post titled 6 Thoughts on Having a Six Million Dollar Son.

Thanks for the answers. Keep up the good fight! Best of luck to Case.

Thank you!

What is the adult life like of someone Hunter Syndrome?

There were traditionally considered to be two "types" of Hunter Syndrome - severe and attenuated, the difference being whether the brain was affected. In severe Hunter Syndrome, like my son has, they generally do not live into adulthood. They experience progressive brain damage and live usually into early teens. The clinical trial drug he is on is an attempt to stabilize that brain decline.

For those with attenuated Hunter Syndrome, they can still have severe physical effects like very short stature, airway and lung restrictions, heart valve damage, carpal tunnel syndrome, joint stiffness and pain. If they get in enzyme replacement therapy (the weekly infusion of Elaprase) while young, a good portion of these effects are slowed or stopped. Since the drug has only been approved since 2006, it's still early to see how a child who starts young will develop into adulthood. Good questions.

How severe is his current mental handicaps? (Sorry if this comes off as rude, had no better way to say it)

It's not a rude question at all. I have to constantly consider such things in assessing the effectiveness of the medication and to figure out how best to teach him. He still has behavioral and learning challenges, but he is actually learning which is miraculous at this stage of his disease given that he was even losing his speech at age three and a half before the trial. At almost nine, he is reading at an early reader level, has a very broad vocabulary, learned to swim and likes to play basketball with his brothers. When people meet him who don't know about his disease, then tend to think he has mild autism. He's generally very happy, full of energy, and is excited to show people what he's learning.

How do you explain your sons medical difficulties to him? Are there support groups for kids out there like him?

Prior to the clinical trial, I didn't really have to - he wasn't at a cognitive level where he could even understand. We did have to manage his medical trauma in unique ways in order to make procedures, infusions, etc. even possible. I did a ton of research and ended up writing an e-book from what I'd learned called Calmer: Medical Events with Cognitively Impaired Children because so many people were asking me about it.

Now that he appears to be cognitively stable as a result of the clinical trial, it's actually gotten more difficult. He often doesn't want to do the medical stuff and asks why, but he can't really understand that he has a disease and that if we don't do all of this, he will deteriorate and die.

It's hard. I sometimes I harken it to the book Flowers for Algernon or the movie Awakenings. I can only hope and pray that the drug won't stop working.

As far as support groups, he loves playing with other boys with Hunter Syndrome - they seem to "get" one another, but we only see each other at some clinical trial visits and conferences. They don't really understand that they have this disease though.

Do you know a kid named Zain that loves pizza?

Yes, I know Zain and his family quite well and was lucky enough to spend time with them recently. He is one special kiddo. I even got a good hug.

Hi Melissa, These questions are rather personal, so feel free to pass. Did doctors find out by testing you and/or your son whether you were a carrier? Did you receive genetic counseling and if so, did you find that it helped? Since it is so rare, my guess is even experienced doctors might not have seen a case like his before.

My thoughts are with you. Your advocacy is incredibly inspiring.

Thank you so much for the question and the compliment. To whom much is given, much is required. We feel extremely blessed and just want to do whatever we can.

Once they found my son's mutation by examining the IDS gene (the gene responsible for Hunter Syndrome), they did test mine as well and I am not a carrier. From my anecdotal experience with other parents, I'd estimate that possibly around 1/3 of mothers (Hunter Syndrome is X-linked, passed down through mothers) are NOT carriers and their child has a spontaneous mutation. There are literally hundreds of different mutation and deletion patterns in that single gene that can cause syndromes like this.

As you can imagine, parents who are carriers often feel unwarranted guilt, and this is even perpetuated by society who sometimes sees a family with several children with a syndrome (or even one) and asks why they'd continue having kids. Of course, most don't even know until the oldest is diagnosed and they've had several children, but even beyond that, these kids are an amazing blessing nonetheless. The worst situation I've had (and wrote about) is when a man - actually a father to a child with Hunter Syndrome if you can believe it - told me that it was my fault that my son was sick.

Wow, that's incredible. I can't believe he would say something like that! I was curious as to how many people are or are not carriers, so that is definitely extremely interesting. I'm so sorry you had that experience with that man and I hope you never experience something like that again! I work at a genetics clinic, and so many people cannot imagine the experiences that people with rare diseases have. I'm always interested to learn more and hear about experiences.

I applaud you for being interested in people's personal experiences like this. Families affected by rare disease are so often in and out of hospitals, clinics, etc that it is a huge blessing to encounter those who are genuinely wanting to help and offer compassion.

Can I see a photo of your son's medial tattoo? Was he anaesthetised for it?

My mother works with autistic and disabled children, and a lot of children with chromosomal abnormalities and she loves to tell me about the kids she works with coming to life through music, art or messy play - what does your son enjoy?

His tattoo was done to identify his intrathecal (spinal) port-a-cath (where the experimental medicine is injected for the clinical trial, the CSF then takes it to his brain) versus his intravenous port-a-cath (where he receives his weekly infusions of a less concentrated form of that molecule which cannot pass through the blood-brain-barrier, but helps his body). Mixing the two up could be fatal. So the word "INTRATHECAL" is what nurses recommended as the best tattoo to make someone stop. They plastic surgeon at the hospital did the tattoo under anesthesia when he was receiving the medicine. A photo and the story is on this blog post: UNC Ink.

Case loves music and physical activities. I've stressed to his school that to learn and play, use music, movement, and manipulatives. He actually rides several ride-on cars all around the first floor (wood floors) of our house. He also recently received a sensory room from Make-A-Wish recently that he loves - see the news story.

I met one of the commercial team members that set the price for Elaprase a few years ago. From their perspective, obviously by the time you get to the pricing stage, you focus on maximizing revenue; however, for the drug to have gone through all the development processes and been introduced to the market, for such a small patient population, the high price is kind of a necessary evil. Is that an argument that you are sympathetic toward? What's your take?

Thank you!

Yes, absolutely. Especially ten years ago when Elaprase was FDA approved, these companies took a huge risk developing drugs for ultra rare diseases like this. It's such a difficult issue. I also see the scientific developments that come from studying rare diseases. The pricing issue has become more challenging now that so many drug companies are coming into the space, slicing and dicing different diseases for personalized medicine, etc. Genetic conditions are the "easier" case for pricing, if there is one. I also wrote about rare disease drug pricing issues in a two-part series: 1. Why I Fear the Bubble, Part 1: The Pricing of Rare Disease Drugs 2. Why i Fear the Bubble, Part 2: A Crash at the Intersection of Personalized Medicine & Rare Disease Research

There needs to be a ban on direct to consumer advertising to prevent unnecessary expenses being added on to costs. I wish your family the best and hope your son has success with his treatments. And take care of yourselves too, a sick child takes a massive toll on mom and dad.

I agree with you to some extent on the advertising, although that appears to be more of an issue with more common diseases. Most often in rare and ultra rare diseases, we have no or maybe one possible treatment options. Only a few conditions at this point have treatment choice and the communities tend to be highly educated on the diseases and treatments.

In more common diseases, I do see the benefit of additional information that advertising has brought, but the pendulum appears to have swung far. I've learned from my experience in rare disease that sometimes patients know their experiences and needs the best, and when they become educated, it's hard when physicians won't listen to them. But most patients with common conditions are not as incentivized (unfortunately, by their own immediate mortality or that of a loved one) to learn and find answers outside of advertising and physician recommendation.

And you're right about the toll on families. I've seen it so much. Thank you, we work hard to stay connected as a family and support one another. I write, which is cathartic as well.

This may be a trivial question compared to everyone else's and you may not know why but is there a reason why World Rare Disease day is on leap day? Does it fall on this day because it's rare? Do you wish it were every year?

Great question. Actually, World Rare Disease Day falls on the last day of February each year, but the years when it falls on a leap year are truly symbolic.

What about the disease makes all patients of it look the same?

I've often wished we knew more about this, but the simple answer is found in understanding the nature of the disease. Hunter Syndrome causes a lack of enzyme that allows cellular waste called glycosaminoglycans (GAGs) called dermatan sulphate and heparan sulphate to build up. So where that the GAGs naturally occur in greater quantities like the skin, heart valves, etc, it builds up similarly in each child. So they often have sweet, thick red lips and puffy, rosy cheeks. And then the downstream effects of the build up them affect the growth of joints and bones causing similar body types. That's my layman's explanation anyway.

Hi Melissa -

1) have you thought much about newborn screening, and if so, are you in favor of it for Hunter syndrome? 2) are you following the Sarepta story regarding their medicine for muscular dystrophy, and the pressure being applied to the FDA by patient groups after their negative report on the study results? i would be interested in your take.

thanks so much for this fascinating AMA!

1. Yes, I am in favor of newborn screening for Hunter Syndrome. I've seen personally that the earlier kids can receive enzyme replacement therapy, the more beneficial. And when gene therapy becomes the norm, kids can hopefully, essentially be "cured" if diagnosed young. The question becomes feasibility for testing for so many rare diseases via newborn screening, so there will at some point be a scalability issue.

2. I have followed the Duchenne drug development since soon after our diagnosis and know many in that community. My take is probably best summarized in a blog post I actually published today that you may find interesting - Rare Disease Drug Approval, essentially, there is a problem with the system of capturing slowing of progression, stabilization, or improvement in rare diseases. I don't have all the answers, but I know some of the right question. Hard issue. Good question.

Wow you an awesome Mother! You do so much to advocate for not only your own child but many others too, so thank you for that! My question is... What signs did your mother see in Case that caused her to suspect this?

Oh thank you, not awesome, just blessed. By the time my mom saw the show, Case was around 20 months old, and he had regular ear infections, adenoid removal, loud breathing, a larger than average tummy, a larger than average head (but we'd had a CT and were given "normal"), pectus excavatum, unexplained and random diarrhea, and his development had slowed (but we'd also gotten the "every child develops differently"). Random symptoms that seemed to be unrelated and that's what I emphasize when I talk about diagnosing rare diseases, especially lysosomal disorders. When kids have symptoms in different bodily systems and accumulate more of them, that's when pediatricians and parents should be suspicious. We were appropriately referred more individual symptoms in the first two years of his life, just no one put it all together and I don't blame anyone. If my mom had not been and RN and miraculously seen that show, I know it would have been at LEAST a year or two for him to be diagnosed. That would have changed everything. He would not have qualified for this clinical trial by then if that had been the case because he would have regressed too far most likely.

Hi Melissa! I used to volunteer for (and later worked for) a horse stable and summer camp that provided horseback riding therapy sessions for both children and adults with physical and/or mental disabilities. I was wondering if you'd ever enrolled Case into a program like that. If so, how did Case feel about it and do you think it benefited him?

Case has been involved in weekly therapeutic horseback riding with an amazing program for several years now. He loves it and has found a good group of 4 kiddos that have ridden together for the last year and he has shown steady improvement in his riding. I believe it's helped with self regulation, following instructions, gross and fine motor control, etc. His stable participates in Special Olympics equestrian events, so that may be a possibility in his future. And he loves mucking stalls as his reward after lessons, if you can believe that!

How difficult are you finding it financially to support your family?

When my son was first diagnosed almost 7 years ago, it was quite difficult. At least one parent's life becomes consumed with doctor and therapy appointments, school meetings, tests, hospital stays, etc. I was doing consulting work back then and luckily could bring it wherever we went but the stress level was through the roof doing all that, plus caring for our two typical children. As time went on, I had to slowly end my consulting practice because of the demands of the clinical trial on top of all that (we were out of state for 9 days/month for the trial). We actually flew out of state for 3-4 days every month for 4 years to stay on the trial. With needing to bring someone with me to help with Case and then other children at home, it was challenging logistically as well as financially. The pharma company pays for the travel expenses, but as we all know, there is a lot more to it than that. Luckily, my husband has a wonderful job and we can afford for me to not work for an income, which is why I do what I do in terms of our foundation, fundraising, awareness, writing, etc. But I recognize that is actually an exception rather than the rule. I work to try to help some of our MPS families access the services their child needs whether it's social services or educational, etc., in addition to challenging FDA and pharma to consider the structure of their clinical trials and how difficult it would be for say, a single mom, to participate. It's amazing how, until challenged with the facts, people don't often think of those scenarios.

Hi Melissa. With so many presidential candidates vowing to un-do the Affordable Care Act do you have concerns about lifetime maximums ever making a comeback?

On a separate note- have you found a good way to best communicate with your insurance company whenever you call in? In my experience the regular joes working the phones are typically ill prepared to understand rare conditions and how they relate to benefits.

Good questions. No, I don't really get concerned about the caps issue but I generally am not a worrier. If there were signs of that, I would of course do my best to fight it, but I've seen no indication that caps will return.

Regarding insurance companies, I generally advise people to connect with case management at their insurance company. Usually, you have to jump through a number of hoops to make that happen, but especially when you need regular nursing assistance or DME, having case management involved who knows the particulars of a child's disease and needs can make all the difference. We had case management until Case was a few years into the clinical trial (he's been on it for over 5 years now), because we had home health for infusions and needed DME for a wheelchair, special needs car adaptations, and orthotics that he previously used. Now, we don't need any of that (that's what you call serious medical breakthroughs), so we "graduated" from case management a few years ago.

Why doesn't God heal amputees?

Low blow. You're pretty messed up in the head.

Oh I can go lower: Why waste so much time and effort on ultra rare diseases if the money is better spent on ensuring that the genetically superior humans have a comfortable and stable life? They're the ones building our future. We have meteor shields to develop before it wipes out mankind. Not Hunter Syndrome.

Unlike your first comment, this is actually a fair one. In reality, whenever a child is born, they carry approximately 60 mutations in their genetic code from what they received from their parents. They also carry 4-5 major mutations that can cause diseases like Hunter Syndrome, Tay-Sachs, etc. So you, my friend, may have or develop a genetically-based condition. Or your child will. Or your spouse. Or grandchild. There will always be genetic diseases. Finding more effective and efficient ways to diagnose and treat them is beneficial to both all of existing and future mankind (unless you stop procreation altogether to prevent mutations, which then there is no future mankind). I don't pretend to think that existing methods like ERT are wholly effective or very efficient, but they are paving the path towards ones that are. Our foundation, in fact, is raising our own funds to support gene therapy research, which is more akin to an actual permanent "cure" though our Project Alive campaign. Patient groups have raised millions of dollars of private money for research that has advanced treatment for many rare diseases, so it's a combination of government funding, private investment, and public, patient-generated charitable funds that drive research.