Ok... so I know

its been too long since our last update.

Wednesday was ERT infusion #3 at Shands.

Unfotunately, we only clipped our original time by about 30 minutes. It seems that despite our attempt to speed up our day at Shands, the people in the Pharmacy department suceeded in slowing us down a lot. That poses a problem with the enzyme. To put it simply, once the enzyme is mixed, it is supposed to be delivered immediately in a 4 hour time frame. Well, it takes precisely 4 hours to infuse it into her once we start the drip. The Pharmacy department did not get the stuff to us until an hour after it was mixed. Not cool.

Out fabulous nurse Kathy (who Gracie has taken a liking to as well :) ) has promised to rectify this situation for our future visits... she has made it her mission, even if that means that she must go to Pharmacy and pick it up herself. Thanks Kathy.

Other than that, it was a good day. Gracie did well and enjoyed some snoozing and playing and watching cartoons and trashy talk shows throughout the day. No reactions so far and her skin is still a little itchy under the bandage, but we're learning to live with that.

So far so good and still on track for our return to Minnesota on April 14th for work-up.

More later, I promise.

Thanks for reading.

ERT #2 - Shands at the University of Florida

So Gracie had her second ERT treatment yesterday, and true to Gracie-style, she did beautifully. On the downside, it was an incredibly long day. :(
We got to Shands at 8 am but we were not called back for anything until 9:45. Yuck. They got Gracie's weight (she's over 19 lbs now! Wowza!) and her BP and temp before they shuffled us down to a room for a once-over exam. More waiting. While we expected to see Dr. Kelly at this point, a PA came in and gave Gracie a looksie before moving us to the Infusion Room. This is a large room with a bunch of big pink chairs where everyone and their brother are getting infused with blood, platelets, drugs... you name it. You'd better believe that each time some else walked in to have their own treatments, they warily eyed us and our potential disturbance.

We met our nurse there, Kathy, who was a doll. We loved her from the start. At that point she was able to call down to Pharmacy and let them know that we had arrived. Apparently, our treatment is so expensive that the Pharmacy folks won't even touch it until it is confirmed that we're on site. Craziness! So crazy in fact that they called the nurse back AGAIN and asked her if she could physically see us as a second confirmation before they would begin mixing the enzyme. Geez, paranoid much?
We were given our place in the infusion room and they finally started prepping Gracie for the treatment. A dose of tylenol orally and then Benadryl by IV. This took forever! 45 minutes to give her the Benadryl. :( Then they follwed up with a dose of Hydrocortizone to ward off any rash.
Finally at 12:30 pm they started the Enzyme drip. It was not until after that was going for about 30 minutes did we meet Dr. Kelly. She's very nice and she was great with Gracie and very sweet so we played a bit and settled in for our long treatment. Gracie snoozed in my arms for about 2 hours while we chatted first with our wonderful nurse and then with a really nice doctor who is doing a clinical study on Prostate Cancer, totally unrelated to Gracie's treatment, she just wanted to hear our story. They were both moved to tears after hearing of our path to diagnosis and the persistence of our beloved Pediatrician, Dr. Cortes. :) Warm fuzzies all around.

At about 3 pm, Gracie woke up and they brought a crib in so we could lay her down so she could play. She did... she played and smiled and babbled her way through the next couple of hours with little complaint. By this time, the room had completely cleared out and the clock is inching toward 5 pm. We saw Dr. Kelly again and she and Gracie had a few minutes of smiling and peek-a-boo before she bid us goodbye for the day. Kathy (our nurse) and Ginny (another Infusion nurse) then came over to change Gracie's dressing. When the original dressing came off, poor Gracie's skin was all rashy and inflamed. Thank goodness it was only in reaction to the bandage and not the Enzyme treatment. They decided to give her a different dressing that should cut down on the irritation and they put it all back together, flushed her lines, and finally sent us on our way at 5:45. Phew.

On to Target for Mommy's retail therapy and then a quick swing by Great Mema's house to pick up a delicious roast for dinner! Yummy! Thanks Mema! We fell into bed around 11- totally beat.

So while things were slow to start and that was quite frustrating, we were generally okay with our treatment at Shands. Kathy was the total bomb and I am happy to say that she will be our Infusion nurse every week. Yay! She also has got a plan in place to speed up our start times for future treatments so that hopefully things will go much more quickly as the weeks go on. Go Kathy!

So all in all, the Shands treatment went fine.

Report Card
Gracie - A+
Shands - B-

Shands needs to thank their lucky stars for Kathy who was great for pulling up their average. I plan to write a letter to her supervisor regarding the great care she has given us.

Anyway, to sum up- long but not too shabby. On the agenda for today- a visit with Dr. Cortes! Wooohoo!

Two More Cents

Here, now! Let me jump on the Shands Stinks Soap Box too, for a minute. You know I can never leave well-enough said alone.


It has been put forth in discussion that the Shands team may expect to get a "by" on blowing the coordination of Gracie's treatment, as they have taken on the management of her ERT as a "professional courtesy" to their colleagues at Fairview, who are going to pull down the lion's share of the cash from this cow by having scored the transplant itself. That idea makes my heart sink.


ERT may be a simple procedure, but it is no shave-and-a-haircut routine. After all, HSCT is also a simple procedure. The chemotherapy to prepare the patient is not revolutionary, either. It's the surrounding care: attention to the patient's inherent and precipitant conditions, and anticipating her evolving needs, that determines the difference between great care and substandard care. Someone who is experienced with Hurler patients and their families, and we are assured that this is what we are getting, would be hip to the reality of Gracie's parents' experience, their sense of urgency, and the degree to which they have become absolute hostages to the scheduling of Gracie's health care matrix.

This kind of ham-handedness is, I think, a symptom of a carelessness that, even in small things, cannot and should not be tolerated when the stakes are this high. It makes one wonder what other, less obvious but more dangerous slips might occur because something just didn't get done. It's an old and often sad tale. Little mistakes can cause big problems for vulnerable patients. Someone on this team really should acknowledge this openly to Gracie's family.

They really should.

Hiccup #1- Mommy's perspective

While its probably not far off from the overall tone of Uncle Mackie's post, I feel the need to post here about this issue with Shands.

When I got off the phone with them yesterday regarding this issue, I looked at my daughter and said, "Gracie, we're not in Minnesota anymore." :(

This is exactly what I was talking about a few post ago when I said I was anxious to leave Minnesota for the next 2 months. As I have told many people since I have been home, I have never experienced the level of care that we recieved at U of MN in my life. Most of my special doctor stuff for myself and my loved ones has been at Shands and the treatment they give seems to have always been the same. I never thought to think of it as substandard... until now.

It angered me so much that Gracie's treatment was so carelessly juggled around by these people. The truth is that its not that hard of a treatment to do. They mix up the enzyme meds, put them in an IV bag, hook it to Gracie's central line, start it, and then monitor her vitals for several hours as she recieves the meds. Really not a tough job. But they will charge our insurance out the yin-yang for it and get paid quite a bit to do this. So I know money is not the issue. Its just carelessness. While my daughter is the top priority and single most important thing in my life, they made it painfully clear that she is not a priority in theirs.

Whats funny is that I never once felt that way in Minnesota. As a matter of fact I often wondered if they had any other patients besides Gracie. :)

My intention is not to have a Shands-bashing party here, its more to show that we don't have to accept this kind of treatment as status quo. I know what healthcare is supposed to be like now- and for my precious daughter, I will not settle for anything less.

I hope that all of our adoring public does the same for themselves.

And to end this post on a good note....


Thats the Peanut enjoying dinner at a nice little Irish Pub we found near the U of MN. We actually were trying to get Italian that night, but this place ended up being pretty yummy for the grownups. Don't worry about Gracie being left out, I think she had sweet potatoes that night. Yum Yum!

Hiccup #1 - Shands Drops the Ball

Well, our first hiccup related to treatment comes to us courtesy of Shands. True to form, they are working hard to prove me right, that they don't always put the needs of their patients first.

Tonight I learned that Shands didn't order Gracie's enzymes early enough to have them delivered for her treatment tomorrow. Sarah had to reschedule for Thursday. Sure it's not the end of the world, but it is a big hassle for Sarah, as she arranged her schedule to take an entire day to travel to Gainesville for this full-day treatment, shuffling other appointments since this is obviously her top priority.

Frankly, it pisses me off. They were given plenty of notice, and holiday or not, should have been prepared. What really burns me is that they don't apologize, take any responsibility for the problem, and make light of it pushing the burden to my sister - who, if you haven't noticed, has enough of her own challenges to deal with. It's amazing how mis-directed some physicians' blame can be (overt or covert), and the fact that they don't recognize the implications.

A simple apology can do wonders for your patient's/ client's trust in and dedication to you, not to mention loyalty, referrals, etc. It takes me back to my posting about ownership of the patient-physician relationship. You are not God, you are a doctor. Finding one who shows a little respect (even if that means dropping the one you have) is a lot better use of time than dealing with someone so willing to waste yours.

My take is this - tell them what you think, make sure that they understand that you need to know that you are their top priority, make sure they know that you need to know that you are their top priority again, and then explore other options to see if anyone else in interested in working with a dedicated family and a rare, interesting, extremely profitable, and challenging patient/condition where the clinical team is really making a difference and improving someone's life. There are plenty of fantastic pediatric specialists in Jacksonville. I don't think it would be too hard to find a replacement. Do you?

Apologies for venting. Clearly missing little Gracie. :(

So I spent some time...

today perusing the MPS forum and reading the journeys of other families struggling with this disease. I stopped reading a few minutes ago and I must say that I am very hopeful for Gracie and her chances at this point. I can't believe how lucky we are to have gotten our diagnosis so early and that we have the opportunity to begin treatment so quickly.

Gracie goes for her second ERT infusion bright and early on Wednesday morning... her first one here in Florida at Shands. The doctor overseeing her treatments is Dr. Susan Staba-Kelly (nice last name!) who I understand previously did transplants for Hurler patients at Duke University. I am excited to meet her and get her take on Gracie's treatment plan.

I am also excited to continue the ERT treaments and watch Gracie's progression. Other MPS parents have noted that they have seen physical changes in their children on ERT, most notably the specific physical characteristics associated with the disease. It makes me wonder if Gracie's looks will change much. I hope not too much because I think my kid is cute as a button as she is, but it will be interesting to see what will happen.

Biology Cheat Sheet: Anatomy of an Enzyme

In deciding whether or not Gracie should undergo ERT along with her HSCT (see the previous biology cheat sheet for explanations of those), we were concerned about something Dr. Kurtzberg at Duke mentioned to us as a caution for combination therapy. She said that Gracie's body would mount an immune defense against the injected enzyme (that is, it would recognize it as not being something Gracie had made herself, and attack it as an invader). This immune activity was given as a reason not to have the ERT treatment in conjunction with HSCT unless the patient were already compromised in terms of lung and heart function and needed the enzyme to help her recover and get in shape for transplant. In Gracie's case, her heart and lungs were pretty healthy, and Duke would likely have gone on with HSCT, leaving off the ERT.

We thought that sounded like a pretty good reason, so Mack asked the docs in Minnesota about it. Their answer seemed like a good one--good enough to convince Gracie's parents to go ahead with ERT, even if the immune response was very likely (according to Dr. K, 90% of patients make antibodies to the enzyme--and that's how you know your body is trying to defend itself against something.).

So the answer the Minnesota docs gave was that, yes, Gracie would probably mount an immune defense against the injected enzyme, since almost all patients do, but that there were a couple of reasons to go ahead anyway. First, the response would probably have mild symptoms, and so would not really affect her overall fitness too much--she might have a little rash, they said (some patients do have anaphylaxis--which is an extreme overreaction by the immune system to the drug--and treatment has to be stopped. Gracie has not shown signs of this so far). The second reason was that, while the antibody does attack the enzyme, it doesn't affect the active site, so the enzyme continues to function just fine, even while the body is trying to attack it.

At that, Noodles asked for a review on enzyme active sites, so here's a quick one:


What is an active site?
An enzyme is, generally, a huge molecule that acts as a catalyst for chemical reactions in the cell. Enzymes make cellular reactions happen more efficiently, and aren't used up very fast (that's how catalysts work. They hang around and help out with reactions, but aren't actually "part" of the reaction--that is, the enzyme is not changed by the reaction it catalyzes.) Typically, enzymes are very specific in the reactions they catalyze, although there are a few enzymes out there that catalyze a variety of reactions--those are cutely termed "promiscuous" enzymes.

Tee hee.


So somewhere on this really big molecule is its active site. the active site is the spot on the molecule that actually does the chewing (or "lysing" in the case of enzymes--get it? Lysosome/lysosomal storage? The names do sort of make sense after a while.) During the breakdown reaction. As we said before, the active site is usually pretty specific, in that not very many kinds of things will bind there. Just the molecules the enzyme is supposed to catalyze in reaction.

If Gracie's missing enzyme (alpha-l-iuronidase) were more promiscuous, the antibody might be able to get into its active site and prevent it from doing its job. Luckily for us, alpha-l-iduronidase only has eyes for iduronic acid--a component of Dermatan Sulfate--the GAG Gracie can't break down. The nasty antibodies can't make it stray from its only mate, no matter how they attack it. This means it will still be able to do its job while under attack by antibodies. Or at least, that's how the story goes.

But what about the immune response? Are you worried about that?
Of course, there are other concerns where immune responses are concerned. They do cost the body energy, and don't feel particularly pleasant for the patient, but we are only just beginning with things that are unpleasant for the patient...try chemo, why don't you? I'm sure there are more specific hazards of immune response, but I am not well versed in them. Any MD's or other health care professionals out there who would like to chime in?

So ERT provides Gracie with alpha l-iduronidase, which is the enzyme she needs to prevent further buildup in her tissues of dermatan sulfate/iduronic acid. That buildup would compromise her body systems, particularly her heart and lungs, and reduce her likelihood for a positive transplant outcome. ERT doesn't protect her brain (remember the blood-brain barrier? see other biology cheat sheets for that, too), but nothing else besides transplant would, either, so we want to keep her as healthy as possible while she waits for a donor match. Following transplant, she will continue with ERT until the graft "takes" which means it begins to make cells effectively in Gracie's body. A stronger heart and lungs will make her better able to stand up to GVHD, the subject of the next biology cheat sheet.

Immediate Next Steps

Well, Uncle Mack is back on the road. I just got to Colonial Williamsburg for my friend Amanda Whipkey's wedding. It should be quite a good time, but I'm missing Gracie. :(

A couple of next steps for Gracie:

First, she qualifies for some sort of speech therapy due to her condition, so we need to get on that stat. If anyone knows ho this works, or how we should get started, we'd love some assistance.

Next, we need to start working on getting housing lined up for Sarah at Ronald McDonald House. I imagine we need to start pulling any strings we can to get that lined up for mid-April.

So, Mandy has been putting her epidemiology hat on and has a theory on the seemingly high incidence of Hurler Syndrome in Northern Florida. It happens all over, but it sure seems like there are a lot of folks in that area who are affected. Thoughts?

By the way...

I just got an A+ on Flushing Gracie's Line! I was very relaxed and I didn't mess up at all! Gracie just sat and played with her fish and barely even noticed! Jimmy is so proud of me. :) :) Woo woo!

Home...

We are so glad to be back home! Gracie is feeling great and we got a pretty decent night of sleep last night. FINALLY.

So I have to note here that my Gracie is officially a great traveler! She really loved flying! When we would take off, she would smile and her eyes would get so big. It was the cutest thing.

So since Uncle Mack keept you all updated about what we were up to in Minnesota, and Aunt Hyster did the clinical teaching of what we're facing with this disease and transplant situation, I am hoping to have a few opportunities over the next few day to sum up how we're feeling. Maybe the more emotional side of this journey we've begun. Since thats the part I'm most familiar with, the part I really know, I guess thats where I will start for now.

I hope I can keep the blog good and alive though... Gracie is definately demanding of most of my attention, but I will do what I can to keep this great blogging momentum going. :)

I'll begin with today. Now that we're home, I'm torn between feeling happy to be back with our family and friends, to anxious because we are still having to deal with and treat this disease away from our trusted and specialized doctors. That is a bit on the scary side. I'm still learning to properly care for Gracie's central line, and we're having to give her some antibiotic drops for her ear tubes as well. Things seemed a bit easier when we were in the frozen north, knowing that the hospital was right across the street full of doctors who know all about Gracie's condition and the particular weaknesses she has. That makes me that much more committed to keeping her line sterile and keeping her generally healthy over the next 2 months... so we can stay away from any other hospitals if at all possible. Fingers crossed.

Gracie is definately glad to be back home. She really missed her jumpy chair while we were gone and she's gotten in it at least 3 times in the 12 hours that we have been back. :) :) Its good to see her in there and happy... it seems normal. Like life before we started all of this.

We have lots of pictures to post from our trip and I hope to get them on here soon. Stay tuned.

And let me say again from the bottom of my heart: Thank you all so much for your love and support. Our families, old friends, church family, my BBB girls, the MPS families, even people we don't know... everyone who has come here and supported us and Gracie through this hard time have a very special place in our hearts. We are so blessed to have you all in our lives. Thank you, thank you, thank you.

Not So Good News from Opthalmalogy

Well, Gracie had an opthalmology appointment yesterday. She didn't enjoy it at all. We learned that she is farsighted, but we don't know by how much. The woman who did the initial (less invasive) exam was really nice. She basically used lots of toys and a cute little soft voice to get gracie to cooperate. Sarah couldn't believe what Gracie was letting this woman do. Gracie did pretty good on this part of the exam.

When she saw the ophthalmologist, she really got mad. He had lots of bright lights which we all know she hates. He used a little thing called a speculum to keep her eyes open. It was really disturbing to look at and she hated it, but it was effective. He got in and got out quickly which was good.

His report was less than ideal. Many of you know about her cloudy corneas, but she also has a tendency to roll her eyes. You may think she gets that from her mom or uncle mack, but really she gets it from her grandma (Noni). Noni knows how to roll her eyes, hahahaha... Just kidding. Turns out she also shacks them left and right too. The doctor thinks that her visual cortex may not be fully developed (yet). These things could cause vision problems down the road. We'll just have to wait and see.

Honestly, right now we are excited just to have a road to be going down. Vision problems are really important, but somewhat second priority at the moment.

Also, I've received some really nice emails from other folks who are parents or otherwise effected by Hurler. Thank you all so much for your support and encouragement.

Heading Home Today

Well, today we all say goodbye to the snow and ice in MN, and head back to our homes. I know we're all excited to get back to family and friends, and to our non-sleep number beds at home. I know that I'm going to miss seeing Sarah, Jimmy, and Gracie every day. I'll have to find something else to keep me busy now that I'm unemployed. :)

Gracie will be getting her ERT treatments every Wednesday down in Florida at Shands. I have no doubt she'll keep doing great. They plan to bring her back to Minneapolis in about 8 weeks (Early April), when she'll finish up some pre-transplant ERT, and then get prepped for chemo and her transplant. The first 1-2 weeks back will be a lot like this week has been. Lots of appointments, consults, tests. Then a week of chemo, and the transplant. Gracie will continue to get ERT in the immediate post-transplant period until she begins creating the enzyme on her own. At that time Gracie will be here for between 3 and 4 months, but at least it will be warmer. :)

Also, I'll surely have less to blog about since I won't be on hand for the next series of treatments. Mandy and I will be doing some research in the interim to try to teach ourselves (and you guys) a little more about this stuff, and Sarah, Jimmy, Noni, and Muntz will have to keep the blog up-to-date on the treatment progress.

ERT Week One - We Made It

Gracie did really well today with the ERT treatment. She didn't have any negative reactions to the enzyme and the nurses thought she did very well.

The building today was really old and sort of gross. It seems they put the research team in the worst areas. The great thing - we had our own nurse, who didn't have any other patients, which was fantastic. Again, we were very happy with the quality of care at Univ of MN.

Keeping Her Clean and Healthy

Gracie has a few post-surgical dressings from her procedures yesterday. There is a small wound where they inserted the central line.

Her mommy is learning how to change her dressings and keep the environment sterile so the central line remains clean. Mommy is very nervous about the lines, about her ability to keep them clean, and about changing the dressings.

There is one big favor that I'll ask of all of you: Her mommy doesn't know I'm doing this, but do your best to avoid the temptation to ask to hold Gracie. Due to the nature of central lines and the implications of any contamination and blood stream infection, I'm sure her mommy will appreciate having few hands on her. Don't get me wrong, Gracie will be perfectly healthy while at home. Her immune system is fine. I'm just taking a "better safe than sorry" route and protecting the lines that lead directly to her circulatory system. Uncle Noodles is a bit of a worry wart!

Gracie still loves kisses, but fewer hands are better. :) If you do hold her for any reason (or as a favor for mommy), please wash your hands well in warm soapy water. A good general rule of thumb for handwashing is to sing happy birthday to your hands while washing. At the end of the song, you're clean, and your hands feel special because they think it's their birthday! :)

First ERT Infusion Going Well

Thanks again for all of the guestbook activities. It's wonderful to know that so many folks are following Gracie's progress and sending us warm thoughts. Our hearts are warm, despite the freezing temperatures.

Gracie is in ERT right now. She's doing great! Daddy's training is really coming in handy, as he understands the lines and ports and dressings, etc. He and the nurse are getting along famously, and he's helping out the nursing staff when they need an extra pair of hands. Gracie is lucky to have him, and his training should make us all ease or worries as they head back to FL tomorrow.

I stepped out for lunch and to post an update or two. She started at 10:00 AM. Like I mentioned before, they start slow; 2 (unknown units, maybe milliliters?) per hour, and assuming she does OK, the double the dose every 15 minutes until she s at 32 per hour. She's been cruising at 32 for a while now, and has about 90 minutes of active infusion left, and then an additional hour of observation.

She has been a trooper so far. Her body seems to be tolerating the ERT very well. We are so proud of her.

Start ERT Tomorrow

Tomorrow is the big day. Gracie starts her first ERT treatment tomorrow AM at 8:30. It will take no less than 3 hours, and today we were briefed on what to expect. It doesn't sound all that bad actually. Some kids have a hives-like reaction, and very few have more serious reactions like like anaphylaxis (difficulty breathing). Other kids are just fine. Risk of reaction is the same for each subsequent treatment. In fact they said that many kids don't have any reactions until the third or fourth session.

They'll give her some tylenol and benadryl before starting, in order to prevent some of these things and to generally make her more comfortable (and sleepy). The staff will check her vitals every 15 minutes throughout the entire process to make sure she is doing ok. They start slow and crank it up after they see how she reacts.

So, that's what Gracie will be up to tomorrow. She begins the road to recovery, in earnest.

PS - I just saw the funniest Dairy Queen commercial. It was a valentine's day commercial with an older couple celebrating their 50th anniversary. They are sitting on a couch you'd find in my Grandma's house in the 70's, talking to the camera.

Wife: It's our 50th wedding anniversary.
Husband: WHAT?
Wife: IT'S OUR 50TH WEDDING ANNIVERSARY

Wife: Each year we celebrate by going to Dairy Queen and getting a cake
Husband: WHAT! YOU WANT ME TO KISS YOUR BROTHER, JAKE?
Wife: YES! I WANT YOU TO KISS MY BROTHER JAKE!!
Husband: ABSOLUTELY NOT! OUT OF THE QUESTION!

Wife turns to the camera and giggles...

Anyway, I thought it was so cute and it reminded me of my parents. Dad, you are almost this bad!

Back in St. Olaf

Boy are we tired! It's relief and adrenaline related tired. I'm tired. I can't imagine how tired Jimmy, Sarah, and Gracie must be. I think we are all due for a nap. Gracie is already getting a head start.

I drove around a bit today, and ran across the Saint Olaf church in near downtown Minneapolis. Just a little tidbit I thought I'd add for anyone who has ever seen the Golden Girls. It must be where Rose went to church... :)

It's 14 degrees today, which is downright balmy compared to recent days (though only 5 with wind chill). We all miss our beds. I've still not found my sleep-number. Not a fan of the beds here at all. I'm currently on "75" but all I want is my pillow top and my dirty old pillow.

Out of surgery and off for the day...

So as Mackie said, Gracie did beautifully in surgery. Hurler children tend to have airway issues which can make anesthesia more complicated. Our Gracie is ahead of the game and with no airway issues, everything went off without a hitch. So Gracie now has a new set of ear tubes and a central line to deliver her treatments and also her new stem cells when that time comes. Yay for no more needles in my Peanut!

Of course with having the central line comes lots and lots of maintenance. And true to Gracie form, I can accurately call it "high maintenence". :) Lots of flushing the lines, changing dressings, changing tube endings, hiding the lines from Gracie, keeping the area clean as a whistle, etc. etc. etc. Of course, we'll go to any lengths for our Girl, so this will soon become a routine walk-in-the-park as well.

We had a quick chat with our BMT Nurse, Teresa. She is heading off to an MPS conference tomorrow, so she wanted to check with us on any last questions we have for her. It seems that they will be trying to get Gracie back for transplant within 10 weeks... actually, it will probably be 9 and Gracie will have her 10th infusion during her work-up. So hopefully it will not be as long until transplant as we originally expected.

So thats a general summary of today's events. More info to come later.

One quick note before I crash...
The sleep study was a total bust. Gracie screamed most of the night because of the stuff stuck all over her body, and Mommy barely slept at all because Gracie would only sleep if Mommy held her. What a nightmare. Even Uncle Mack in his dead-to-the-world sleep heard the Peanut protesting the sleep study. I can only hope that we did not have neighbors on the other side of our room. :(

Gracie's Report Card

Here is Gracie's report card to date:

Audiology D Gracie failed her Audiology exam. We'll get em next time.

Neurology A She has great reflexes, and flirted a lot with the teacher. Naughty little thing

Neuro-psychology B She's great with blocks and stuff, but she was tired of playing at the end of the day

ENT A She did great with the doctor, and the tubes she got will help her on the next Audiology exam

MRI A She was sleeping, so she was very still. That's all it takes for good MRI

Cardiology C She has some build up and leakage in her valves. Nothing too serious yet, but makes us happy she'll be starting treatment tomorrow

Surgery A Gracie shined in surgery. All went well and her mommy and daddy are with her while she recovers.

Good job gracie!

In Surgery

Gracie is in surgery now. It's 8:30 AM in MN. Sarah just called me to let me know everything is going well so far, and she and Jimmy are trying to eat something quickly. She will be in until 11 or 11:30.

True to form, yours truly overslept by 2 hours even though there were two alarm clocks screaming at me right next to my head. I need my own sleep study to determine why I'm such a sleepyhead. Bad Noodles!

Wish us luck!

First Anesthesia Tomorrow

Tomorrow AM at 6:00, Gracie will have a couple of minor procedures. They'll put her under to insert a central line to her jugular vein, where they will administer the ERT treatments. Having the central line will prevent multiple needle-sticks for each time she has treatment.

While she's under, they're going to insert PE tubes to drain the fluid in her ears. This will both prevent inner ear infections and significantly improve her hearing.

Gracie's Sleep Study

Some guy came down tonight to set up for a sleep study. To be honest, we are all a little on edge right now. It was weird having the guy set up medical equipment in the hotel room. They are testing her for sleep apnea and other breathing issues that are common in kids with Hurler. Oh well, we've gotta do what we've gotta do.

Things feel like they are starting to move rapidly, and as great as today was, it was ten times as frightening. Keep us in your thoughts tonight and pray for no apnea. We're going out for Italian tonight to try to ease our minds with comfort food, and maybe a glass of wine (or three).

ERT and Transplant - Our Final Answer

To be completely honest, Gracie is at relatively low risk of having complications from the transplant. That said, how low can risk can one really be when fewer than 9 out of 10 kids survives the procedure?

Here is a list of contributors:

1. Prevention. When taking ERT, risks of pulmonary problems post-transplant are diminished. Taking a “risk averse” stance. This transplant procedure is risky enough. We want to remove as much risk as possible. Preventing pulmonary issues related to transplant. Most kids that experience serious problems experience bleeding in the lungs after being on a ventilator. Pulmonary issues, as referred to by the physicians. Most of those kids already have other pulmonary issues prior to transplant.

Gracie does not. And by taking ERT treatments, Gracie will not develop pulmonary problems (or other likely problems with tonsil and adenoids, etc), either before transplant or while waiting for the transplant to work (engraftment).

Dr. Tolar thinks that ERT “absolutely” benefits even healthier kids by protecting the lungs and other organs from GAG build-up.

2. Interim relief. As Kendra (Dr. Byoraker) relayed, “ERT is giving Gracie something that she needs, but doesn’t have.” The enzyme will help Gracie rid her body of the sugars that would otherwise accumulate throughout.

3. Both Kendra and Dr. Tolar expressed very directly how they would handle the situation if they were in our shoes. They would go forward with ERT. Although there isn’t sufficient data to prove that ERT will make a difference, Kendra and Dr. Tolar shared their beliefs in the treatment based on empirical evidence of the handful of babies and families that have gone through it. At the end of the day, ERT is a very low risk intervention.

Here are answers to questions that were leading to our reservations regarding ERT:

1. If Gracie takes the ERT, won’t that delay time to transplant? Yes, it probably will, but not by as much as we thought. The woman at Duke told us they can find a donor in 10 days. While technically true, she was only giving us part of the story. According to Dr. Tolar, there is a lot that must happen after the donor match is identified but before the transplant takes place. He said that it generally takes around 6 weeks, and they started last week for Gracie.

The research protocol calls for 12 weeks of ERT prior to transplant. To complete the protocol would mean delaying by 6 weeks at most. If we want to proceed with transplant as early as possible, we can always remove Gracie from the protocol once the donor cells are ready. There shouldn’t be a negative effect on her outcomes.

2. If Gracie takes the ERT, could that negatively impact the transplant, meaning lower engraftment rate or lower enzyme production rate once the donor cells take over? Dr. Tolar loved this question, and his answer is (emphatically) “no.” Again, the physician at Duke gave us pause when she warned us of the antibody reaction to ERT that happens in almost every child. Our worry was that this antibody reaction would influence transplant success. Dr. Tolar said that they had the same worry prior to offering combined treatment. They’ve tested and found that although there is an immune reaction and you will find antibodies, they don’t target the “active site” where the enzyme is produced (Mandy, there might be room for a biology cheat sheet on the active site).

Even though this question is at the root of why Duke doesn’t do ERT-combination therapy, Dr. Tolar said that the questions have been answered and are no longer relevant concerns. He said that there is no reason to worry about that.

Unfortunately, I left my notes in the stroller, which is still in the hospital, so I’m not 100% sure I am accurately recalling all of the important details that inform the emphatic no.

3. If Gracie takes the ERT, will that influence her chances of getting a severe case of graft versus host disease (GVHD)? Again, the answer is no. ERT has no positive or negative impact on GVHD.

I hope this is helpful and not overly complicated. This was a very spirited discussion that we had with Dr. Tolar and his team. They loved our questions and preparation, and genuinely are most concerned with helping us find the answers we needed to make a decision. I’m very confident that this is what is best for Gracie, and for our family. Thanks again for reading.

Miss Cord Blood America

One of the primary reasons they've decided to move forward with ERT is the time required to find an adequate matching donor for Gracie's cord blood transplant. We got a good run down of how this works today, and it made me think of Miss America.

First, they test Gracie's blood to determine all of the Gracie specific nuances of her blood cells. They look for special things in/on her DNA called "alleles" that need to match the donor alleles.

The start with a database full of thousands donor cord blood specimens. All of them are competing to match Gracie. Those that match her alleles are the best candidates. Of secondary concern is the volume available, or the absolute number of cells that can be infused. More is better.

After time and lots of testing, they pick a winner, Miss Cord Blood America, and claim it as Gracie's. In the event something should happen to the winner, they select a first runner-up, also reserved for Gracie, that will take over as Miss Cord Blood America if the winner is unable to fulfill her duties for any reason. :)

Question for Susan from Jacksonville

Susan, I saw that you live in Jax and have 2 children with hurler and come to U of MN. I'm so happy to hear that you've had great outcomes! Yay!!!

Sounds like we should definitely keep in contact, but I couldn't access your email address via Gracie's guestbook. Can you please email me at mgkelly@gmail.com so I can have Sarah contact you? I'd love to know where you go in N. FL for treatment and routine check-ups, etc. It would be great to tap into any resources with Hurler experience in N FL. Thanks!

The Quick and Dirty Summary - 2-11-08

First, thank you so much for signing Gracie's guestbook. She and her family are so appreciative of your love and warm thoughts and prayers. It warms our hearts to read everything there.

After a day of rest yesterday, we ramped up quickly today. I'll be making a number of individual posts to summarize our meetings so far, but here is the quick and dirty summary:

We've had three exceptionally valuable consults today.

1. Neurologist - Dr. Charnas. He was a bubbly guy who liked to make jokes at his own expense, most notably his hair loss. :) He seems like an incredible physician. He had a medical resident (student) with him that I believe is Gracie's first true love. She couldn't get enough of this guy! That said, he is married, so we'll have to steer her away from the home-wrecker lifestyle. :) Gracie did great on his exam. To date, everyone is in agreement that she is in great condition relative to other kids they see. Thank you again Dr. Cortes. Many times over we've heard from these physicisans that you deserve some sort of medal. :) More to come later.

2. Neuropsychologist - Dr. Bjoraker (call her Kendra). She reminds me so much of Marsha Kazmierski. She is easily my favorite person we've met to date. Hmm. Perhaps I'm in love too... haha. I had about 20 minutes one-on-one with her, and she discussed and advised me like a friend would. Everyone has been amazing, but this woman takes the cake. One reason she was so valuable: she recently had a son in the hospital with a very serious condition. She knows exactly the kind of advice and insight we need, and didn't hesitate to provide her perspective. I'll share more later.

3. BMT Intensivist - Dr. Tolar - Gracie's second consult (my first) with the guy who will be doing the transplant. This was unscheduled, but he made time for us to ask and answer questions. This was a very big conversation. I'll summarize here by saying that I honestly don't think Gracie could be in better hands. This guy won my trust. There is much more to come about this consult.

In aggregate, these conversations resulted in Sarah and Jimmy's decision to move forward with ERT, as initially planned. A more detailed explanation of exactly why will come later today so keep posted. I am so so happy we chose to come here. Gracie will receive the best possible care in the world, right here in Minnesota.

Gracie has appointments all afternoon, so I'm sure she will be exhausted at the end of the day.

PS - Despite the cold, we went out for a fantastic, delicious dinner last night at Joe's Garage. Both Sarah and I had mashed potato bowls piled up with delicious stuff. YUM!

Another day of Doctor stuff...

... on my Peanut's 7 month Birthday. :(



Happy 7 months, Sweet Baby Gracie. Mommy and Daddy love you so very much.

Break It Down For Me, Brother!: ERT and HSCT

So here we go! What is Gracie in for?
I thought you'd never ask! If we follow the study protocol (which is still up in the air, as far as I know), Gracie will have 12 weeks of Enzyme Replacement Therapy (ERT), followed by Hematopoietic Stem Cell Transplant (HSCT, or Cord Blood Transplant), and then, more ERT until the graft catches up.

Umm...Right. Let's start with what's Enzyme Replacement Therapy?
Enzyme replacement therapy is, like we said in the last cheat sheet, the introduction of alpha-l-iuronidase, the enzyme she's missing, into her bloodstream. It gets in there by injection, once a week, and is taken up by all her body cells, except those in her Central Nervous System, which is behind the blood-brain barrier (also discussed in the last cheat sheet, but there's more on it here, too), so the injected enzyme can't get to those cells.

What will that do?
The enzyme in her bloodstream will be taken up into every cell in her body across the capillary walls. These walls have holes in them that let the stuff cells need (like energy molecules, drugs, hormones and the like) get from the blood into the cell. The holes are called "fenestrations" which is a fancy term for "windows". Biologists love their fancy terms for things. :-)
Inside her cells, it will be used to break down the Dermatan Sulfate (the mucopolysaccharide, AKA "GAG" that is collecting in her cells) so that it can be "cleared" or removed from the cell. The broken down pieces of the GAG will go out into the bloodstream and out of her body through the usual channels, like they are supposed to. This therapy will keep her body cells (not brain cells) clear of the offending Dermatan Sulfate temporarily until the HSCT can be done and her cells can start making their own enzyme.

Why can't it get to her brain cells?
Remember the "fenestrations?" The capillaries that go to the brain and other parts of the CNS don't have them. Instead, they have "tight junctions" to hold the vessel-wall cells together, so that only small molecules, or fat-soluble molecules can get across (like oxygen--and alcohol!). The idea is to protect the brain from infections and poisons, but it often protects the brain from medicines, too.

But HSCT can get the enzyme across the blood-brain barrier? How does that work?

The blood-brain barrier keeps out most things that are dissolved in the water part of blood (which is mostly water, anyway) but allows some things that can be dissolved in fat (like alcohol and caffeine) to cross. You can also get molecules across inside a cell membrane. People have been trying to sneak drugs across the blood-brain barrier for a long time, using complicated engineered "transporters" which are supposed to act like cell membranes, but so far haven't worked very reliably. HSCT works on the genius idea that, if you can inject cells from someone else, cells that make the chemical you need, then the blood-brain barrier's really no problem! You can just put the new cell with the enzyme (or other necessary product) into the body and let it go across the BBB as if it belonged there! Furthermore, Hematopoietic Stem Cell Transplant is the implantation of cells that generate more cells (making new blood cells is called "hematopoiesis"--another 50-cent biology word)! That way, the good cells keep getting made without the need to inject any more! Genius!

Boy, that really is genius! And you can infuse it in 15 minutes? So what's the big deal?

Well, every genius idea has to get over a roadblock or two, and there is a substantial roadblock here call the immune system. The immune system is another brilliant idea the body had to protect itself from invaders. When the body detects a cell that doesn't belong to it (like a bacterium, a virus, or somebody else's blood cell) it sends special immune-competent blood cells (macrophages) to go attack it, kill it, eat it, and expel it from the body. It is an extremely effective system that allows people to survive all kinds of germs and bugs that get in, but it's not a very nice way to treat a foreign blood cell that's just trying to help you out. Sadly, the immune system can't tell the difference.

Fortunately, there is a way out of this connundrum. Unfortunately, it involves blowing out and resetting Gracie's immune system. More on this, and what makes HSCT so risky in the next biology cheat sheet.

As promised...

I mentioned earlier about an MPS/ML Forum I stumbled across in my early research. Although I have only made a few posts there, it has already become an invaluable resource for me. Basically, its a messageboard forum for parents, caretakers, and family members of children or adults with MPS. This site deals just as much with the emotional aspects of living with and battling these diseases as the clinical, so access is restricted to those directly involved with the disease. It is an extended family for those of us who face these hurdles and you know when you post there that these people know exactly what you're going through.

If you happen to find this blog while searching for information on Hurler Syndrome or MPS in any form, give this forum a try. You'll find a kind of support there that no one else can give you. You are not alone in this. There is hope and fellowship in community.

http://www.mpsforum.com/

New! Fun Blog Toy!

Please sign Gracie's guestbook when you visit, and if you can think of a fun keyword to bury in your message, we can continue to enjoy a chuckle at Google's expense.

Thanks, Uncle Mack, for precipitating the cheerleading ads at the top! :-)

Don't Doubt a Mother's Intuition

On Friday, one of Gracie's pee-pee tests showed an elevated white blood cell count, which could indicate an infection of some sort (which would require antibiotics (and risk of thrush) and potentially delay treatment, even if only by a few days). The doctor had us take another urine sample to the lab on Friday night to confirm, but went ahead with antibiotics just in case.

Sarah was not excited about the antibiotics due to the risk of thrush, and wasn't convinced that she had an infection. So we let the doc know we wanted to wait until the results came back. They just called and the results were negative. Sarah = right. Avoiding the antibiotics in the process. YAY!

Colder than a Welldigger's Ass

Hi all,

This is officially the coldest weather I've ever been in. Unbelievable. A good day for Gracie to be inside! Although her mom and dad have the cutest little get up to keep her warm. Looks like a big wool sock, and she fits right down inside. :)

One good thing about Minneapolis, is that you almost never have to actually go outside. They have what's called "a gopher trail." A network of underground and above ground covered walkways. They were thinking ahead. I bet summer here is beautiful though. :)

Thanks for the Comments

Dear family and friends:

Just wanted to send a quick thanks to all of you who have emailed and left comments on the blog. It's motivating to know that people are reading it, and that keeps us posting more and keeping you all informed. In fact, it's the only way we know anyone is reading it. :)

Please feel free to comment when you want to, even just a hello and we're thinking of you. It's great to hear from you.

xoxoxo

Somewhere in Middle America

I've been singing that old Counting Crows Song all day, "Omaha, somewhere in middle America. Get right to the heart of the matter, it's the heart that matters most. You'd better turn your ticket in, i-i-in, or get your money back at the door." See, stuck in my head, even though we are nowhere near Omaha.


The Mall of America was quite a diversion. Not only is it huge, it also has an indoor amusement park. Here is a picture of the ferris wheel. There is also an underground aquarium, gigantic lego-land, a log waterslide, and 2 rollercoasters. Weird, and a little unnerving to have all of those carnies hanging out in the mall. The Mall of America has the highest baby strollers per capita in the world. So many, that Sarah had to wait in line for the baby changing station! Oy vey!

We had a good bit of retail therapy today. We all bought what we needed and a few additional things. We were there all day, and only walked 1/2 of the mall at the most! Much of the mall left for another retail therapy trip.

Gracie also really enjoyed the visit today. She was such a great little girl, and she helped Sarah get some retail therapy, and eer picked up a few items for herself. :) Here she is with her new bear that Uncle Chris sent her in a care package.

The highlight was our trip to Orange Julius. Yummy! Took us all back to our youth and trips to the Oaks Mall in Gainesville. Tomorrow, the temperature is supposed to be -12, and that doesn't include wind-chill. Yipes!

Where is my Lysosome?

And what's wrong with Gracie's?

For those of you not sitting in on doctor's office visits, here's the (relatively) short answer. Hurler Syndrome is one of many nasty disorders in a class of diseases called "Lysosomal Storage Diseases". These are just one category in a larger group of genetic problems known as "Inborn Errors of Metabolism."


Error? What error?

As the name suggests, the error is in a chemical that operates out of the lysosome on the catabolic side of cellular metabolism. That is, it's a mistake in breaking down a chemical (catabolism), as opposed to a mistake in making one (anabolism). Specifically, it's a mistake in breaking down a chemical called a glycosaminoglycan (a GAG), which is one of the chemicals that the body uses to make bone and cartilage, and other kinds of connective tissue. Chondroitin Sulfate is an example of a GAG, probably the one most people have heard of, but it isn't the one that Gracie is unable to metabolize. She is unable to break down another one called Dermatan Sulfate.

Why can't she break down Dermatan Sulfate?

Enzymes break down chemicals in the cell. If you're missing one, you have trouble. A simple example is lactose intolerance. If you're lactose intolerant, you don't make sufficient lactase (the enzyme) to break down lactose (the the milk chemical), and you get gas and diarhhea from milk products. Dermatan sulfate is a big molecule with lots of little components, one of which is iduronic acid, which is broken down by alpha-L-iduronidase (see how the names match up?). alpha-L-Iduronidase is the enzyme Gracie is missing, so she can't break down the GAG, so it accumulates (gets "stored") in her cells.

Was it something she ate?

Nope. All of your your cells make the GAGs and break them down. You can't prevent MPS by not eating GAGs. Your body just makes them, no matter what you eat, because you need them to make bones and cartilage and membranes and stuff. You have to have them, and you have to get rid of them, too. So, even though it's called "metabolism" it's not something you can control through food, like the Atkins diet or something. There are some inborn errors of metabolism, though, that can be controlled by watching your diet. (PKU is a good example. Stay away from phenylalanine from birth, and you're ok. Otherwise, you're in big trouble.) Unfortunately, MPS is not one of them.

Why can't she just take medicine for it?

ERT (enzyme replacement therapy) is just that. It's as simple as it sounds. You put alpha-L-iduronidase into her body and it goes into her cells and breaks down the iduronic acid in the Dermatan Sulfate and everything works like it's supposed to. There's only one problem.

The blood-brain barrier

The brain cells are protected from things like infections and poisons by a layer of cells that are bound to each other more tightly than those in the bloodstream in most of the body, and that is the blood-brain barrier. As a result, only very tiny molecules can squeeze through these tiny spaces between the cells. A bacterium is way too big, and the alpha-L-iduronidase enzyme is also too big. this means that you can't get enzyme to your brain cells by injecting it into the body, unless you put it "behind" the blood-brain barrier. You could do this with a spinal cord injection, but someone died in a clinical trial of this method, so they're not doing it anymore until they find out what happened.

HSCT (hematopoietic stem cell transplant), or cord blood transplant, is a way of introducing enzyme-producing cells into Gracie's body, so that she can make her own enzyme. Then, it will be made in all her cells, and it won't have to cross the blood-brain barrier as a chemical in the blood. This means that she can get enzyme made in her brain cells, and deterioration of her brain will stop.

Isn't wikipedia amazing?

Ahhh... A Day Off

Hi all. I hope all is well wherever you are and that it's warmer where you are. We got a light dusting of snow this AM and it's freezing. We're headed to the Mall of America today - Chris told me that it's the 4th largest tourist attraction in the US. Even if that's remotely close to true, very sad... I'm taking a camera so we can document what America looks like. My friend Derrik wants to see a mullet.

We need some time out of the hotel. I need something to keep my ears warm, Jimmy needs a cord or his blackberry-thing, and Sarah needs baby butt paste. Yay!

We all slept like a rock last night, even in these crappy sleep-number beds. Lindsay Wagner may be a 65, but I don't think my sleep number exists, and pretty sure I don't have patience to find out. Basically, they remind me of fancy air mattresses. I won't miss the Radisson beds... That just shows how exhausting yesterday was for us.

Welcome to the frozen north!

Here were are. In Minnesota. Um yeah, its cold.

But despite my chilly feet and cold hands, I can tell you that I have a very warm heart. We met with many of the people here at the Transplant Clinic, and with each meeting or appointment, I became more and more sure that we are in the best place we can be. Everyone here is so nice. They're kind, friendly, accomodating, and full of information. So much so that I think my head is about to explode. We still have some huge decisions regarding the ERT/Transplant route to make and before we do we need even MORE information, but truly and for the most part, I am at peace with this process and I know that Gracie's chance at life is as at its best because we're here.


Gracie has been exceptionally happy and well-behaved since we've been here. She has hit 2 major milestones in the past 3 days... first, she audibly laughed out loud. I must say, thats the best sound I have ever heard in my life. My heart nearly bursts every time I hear it. Also, she finally rolled over!!!! Woohoo. Gracie rolled from tummy to back last night to the sounds of wild applause from Mommy and Daddy and Uncle Mack. What a celebration! It seems that the subzero temperatures and the midwestern landscapes sit well with her. :) We miss home and family and friends though and we're looking forward to getting back to the warmth and comfort of the sunshine state soon. :)



I have lots of info to post, especially the online forum I found for MPS folks, but I have my little Peanut to tend to at the moment. So it will have to wait for another post, but I'll leave you with this to make you smile.

All bundled up and ready to face the weather! :) I promise we'll try to get more pics posted soon. Stay tuned.

Defining Transplant "Success"

Really interesting insights from Dr. Whitley about successful Hurler treatment.

Is success defined by the degree of engraftment (the percent of total cells that are donor cells), or the enzyme activity of the donor cells relative to a "normal" kid?

According to Dr. Whitley, in Hurler patients, enzyme production yield is less important than percent engraftment. In most patients, even 25-50% enzyme yield is sufficient for success. Partial engraftment is sub-optimal, but not the end of the world. Since Gracie is small, degree of graft uptake is more likely to be higher.

We keep hearing an anecdote from numerous folks about a 21 year old in North Dakota, who is living a normal and happy life (he was here for a check-up last week). Turns out his graft was only partial and his donor already only had 50% enzyme yield. He, as a result has about 25% on the enzyme yield of a "normal" kid. Yet, he still lives a great life.

So, I'm confused now, how about you? :) Really interesting and encouraging though.

Part II - Feb 8th, ERT or no ERT - Hanging with Dr. Whitley

Dr. Whitley is an amazing guy. He's the geneticist we met with at the end of the day today. This guy knows his stuff, and is one of the pioneers in Hurler research. I had a whole list of questions for him, and he was patient with us, and stayed with us until well after 6:00. I'm sure he was expecting a quick 30-45 minute chat. We surprised him.

He was really impressed with Sarah and Jimmy, especially how much research they've done, and how informed they are. Essentially, the conversation boils down to one question: Should Gracie have enzyme replacement therapy (ERT) prior to transplant. I'll try to break down the options now, but it's hard when I can't draw pictures for you.

Option I - Transplant only. No ERT. Upside: Speed. Downside: We're trying to decide if the benefits of ERT make a difference. It takes about 10 days to find a donor for cord blood transplant. That means Gracie should be able to start chemo and transplant by the end of February.

Option II - Intravenous ERT for 8 to 12 weeks, then transplant. Upside: Potential benefits include rapid reduction in any potential peripheral problems, and better preparation of the pulmonary system for the chemo and transplant process. Downside: Delays actual transplant until Mid-April (2 months later).

Option III - Intrathecal ERT then Transplant. Intrathecal means they deliver the enzyme via spinal tap, directly into the cerebro-spinal fluid. Upside: More direct delivery mechanism, that should accelerate parts of recovery. Downside: Enrollment in this clinical trial is currently frozen. Apparantly, a child with Hurler-Scheie being treated on option III at UCLA died unexpectedly. Signs suggest that the death was not related to the intrathecal therapy, but until the full autopsy results are available (6 weeks) they are taking precautions by closing enrollment.

My interpretation: Sounds like ERT is great for bigger kids with Hurler-Scheie (a milder form of of the disease that presents later in life), since it helps with many of the non-neurological issues. ERT doesn't cross the blood brain barrier, so it doesn't correct the neurological deterioration - only transplant will help that.

According to Dr. Whitley, Option II (above) is primarily for kids who experience respiratory and pulmonary problems when they first present. Because Gracie was diagnosed so early (THANK YOU Dr. Cortez), she has no evidence of those specific problems. In other words, I'm leaning toward ERT being a "nice to have" and not a "need to have" for Gracie.

It doesn't seem like ERT will do any harm, but the question is, will it do enough good? In a nutshell, is it worthwhile to do ERT even though it will postpone the transplant by 10-12 weeks? We'd love your opinions and feedback here. We're having a difficult time with this particular decision.

Part I - Feb 8th , A Long Day in the Hospital

Hi Everyone!

We just got in from a long day of tests and consults at the University of Minnestota Medical Center, and we're still not quite finished. I'll be dropping off one more urine specimen this eve for some additional tests. Then it'll be martini time. :) Gracie was soooo good today. She's a tough broad! I think Hurler and the transplant will be no match for her.

If you want to know how complex and entirely consuming this disease is, we'll have to post the schedule and the list of different folks Gracie is meeting. I'll give these folks a lot of credit for coordination thus far - at least for the first two days. Everyone has been extremely accommodating. Impressive stuff.

Oh, and anyone interested in their systems infrastructure - they use Allscripts in the outpatient clinics and Navicare in the OR. They have PACS but I didn't catch a glimpse of it yet, and also no real interaction with the inpatient systems yet. :)

Her first appt was in audiology. She failed the audiology test. :( (Her first and hopefully only "F") Next we went to see the ENT. Her tonsils and adenoids seem normal, so no planned intervention there. She has fluid in her ears so she will get tubes inserted on Tuesday. The ENT doc was an interesting character. I liked him, but he kind of reminds me of some goofy cartoon character - cant pin it down right now though. Seems like a really sharp guy, but just socially awkward enough to seem embarrassed and/ or bored and/ or uncomfortable each time he starts to speak. Rarely makes eye contact, etc. We couldn't help but chuckle when he left. Regardless, he's helping our Gracie, so he's all good in our eyes...

Next we went to anesthesiology. They needed more info than we had before confidently proceeding with anesthesia. Until they get MRI results, xray results, and echocardiogram, etc. Until then, they assume the worst to be safe. They'll get those results soon though. It was still good to meet them. It's clear they understand the unique issues and challenges from Hurler, including the immature cervical vertebrae issues I mentioned previously.

Next was the echocardiogram - it's like a sonogram for the heart. It was cool to watch on the screen. Gracie was very helpful through part of it. She wanted to hold the sonogrammer (?) and tried to eat it too, of course. Then she decided it was time to scream. That lasted for the last 3 or 4 minutes of the scan.

I'm trying to keep these posts somewhat bite-size and digestible, so they don't overwhelm me or you, and so you can read them without too much time investment. That said, I'll post separately to discuss our last meeting with the geneticist, Dr Whitley. He was part of the first bone marrow transplant for Hurler's at Univ of MN, and has been a leader in Hurler's treatment for many years. The meeting lasted at least 3 hours, and was really informative and started a host of questions for us and for the doctors to consider when making a treatment decision. Stay tuned.

Fifteen Minutes!

I forgot one thing that shocked me: The actual transplant only takes 15 minutes! Unbelievable. Technology is amazing. I'm so thankful that we have this opportunity.

What's for Dinner!

We are in a nice little area near the university. Lot's of food options. Tonight we went to a noodle house for delicious noodle treats. Gracie had pears, but was disappointed that they weren't home-made. :)

She looked so cute all bundled up. We'll have Jimmy post some pictures.

Summary - Conversation with Duke

Mandy and I spoke with Dr. Kurtzberg at Duke today. I didn't know at the time, but one of my former co-workers told me that Dr. Kurtzberg did a bone marrow transplant for her brother who had brain cancer. He was 10 at the time and now he's a scientist! :) She gave us a lot to think about, but also reassured us that Univ of Minnesota is one of only two right places to be. Here are the critical insights from our chat:

1. Treatment at a place with lots of Hurler experience is critical - Seems there are a lot of little disease-specific nuances that require special attention. For example, two vertebra are not quite right in Hurler kids, requiring special head positioning during treatment to prevent respiratory complications.
2. Good news: Hurler kids tolerate the chemo treatment relatively well - According to Dr.Kurtzberg, most don't even get all that sick/ nauseous during the 9 days of chemotherapy. They do lose their appetites, but IV feeding takes care of that.
   
3. Cord blood sounds better than bone marrow - Because it comes from newborns, there are a lot of non-blood cells in the cord blood that may help with other development issues. For example, there are neurons that can help with neurological development, etc. Bone arrow doesn't have these benefits. She also said that cord blood yields better outcomes. Some marrow kids end up with more orthopedic problems, and she sees a lot of "normal" cord blood kids. Finally, it only takes 10 days to find a match, so that won't hold up treatment
   
4. Younger is better - Not just because you head off a lot of the degenerative activity, but also because you can infuse them with more cells (not sure how this works...)
5. Kids have a much harder time in the month following transplant - that first month is critical, and we'll be praying and praying - you should to! The first two weeks, her blood count will be very low
6. Lots of tests will need to be done to make sue Gracie has no viruses before she starts chemo. Apparently, that is what causes most of the complications.
   
7. Graft versus host disease (GVHD) occurs in about 20% of cord blood transplants - it's serious in about 5%. They have a lot of treatments for this.
   
8. The big new question that came up is around the combination of enzyme replacement therapy and transplant. She is against it, although Gracie is scheduled to start it next week. I didn't get the details of why, so I hope that Mandy can chime in with a post explaining the issues. Needless to say, we have a new round of questions for the docs at Univ of MN.
9. Another question we want to answer is the difference between successful transplant (meaning the graft "takes") and the level of enzyme function. Most studies focus on the former as the success metric. I would say that from a quality of life perspective, the latter is probably more important.
   

Sarah, Jimmy, and Gracie had a great day at Univ of Minnesota, and they have been really impressed with the care team thus far. Given that we are here, and that they like it, I think the plan is to move forward with treatment in Minnesota. Duke sounds pretty good too, but we had a couple of reservations based on the call.

Other great news, our cousin Tracy knows a pediatric neurologist (Dr. PeePee, she calls him) in Minneapolis who will give us the good, bad, and ugly of all of Gracie's physicians. Thanks Tracy!

Another interesting note: Sarah found an online group of families who've been through this before. I hope she will summarize her experience with that, because it sounds like a terrific resource. They seem to also really support the Minnesota option.

We're all cautiously excited. Gracie will get a central line across the next couple of days, and pending our grilling them, she will start ERT next week. Much more to come!

Baby It's Cold Outside

I arrived in MN this afternoon. It's about 10 degrees and everything is covered with snow. Welcome to the great white north, Gracie! The hospital and hotel are near the university, so there is a lot of activity around, people milling about, etc.

I just spoke with Sarah, and it sounds like they've had quite a day of meeting doctors and running tests. Gracie is pretty tired and was letting Sarah know while we were on the phone. They still have a few more meetings but should be able to relax around 5:00 central time. Once I get a full run down of the activities, I'll be sure to post here.

Mandy and I have a conference call with the folks at Duke today at 4:00, so wish us luck! Take care a stay warm!

Duke vs. University of Minnesota

Big decisions: I think we are currently leaning toward Univ of MN, but deciding on the right place is tough. We have criteria beyond what is listed below that incorporate a lot of care coordination needs and multi-specialist care, beyond just the transplant itself. This is still not a fully developed summary, but here is a brief comparison of the Duke and University of Minnesota programs:


Duke:

• Heavily favor cord blood over bone marrow for transplantation
• Do not offer combination ERT/transplant. They have a clinical rationale for this.
• Experience: Transplanted >50 young children with MPS I and >160 children with metabolic diseases
• 85% transplant survival rate

University of Minnesota:

• Offer both cord blood and bone marrow for transplantation
• Start ERT prior to transplant, in an attempt to head off non-neurological deterioration while searching for a cord blood / marrow donor match
  
• Transplanted >80 kids with MPS I. Not sure of other metabolic patient transplant experience.
  
• 88% transplant survival rate

Tomorrow Sarah and Jimmy will be talking to the transplant physician, so they'll have an opportunity to ask questions, and discuss the pluses and minuses of combination ERT/ transplant treatments. We'll also try to catch up with Duke tomorrow to find out more about the treatment philosophy there.

Promising News from Duke University Physicians

Today I got an email from Dr. Joanne Kurtzberg, a physician at Duke University who also specializes in treating kids with Hurler's. This is one really encouraging paragraph from the message:

"We have transplanted >50 young children with MPS I and >160 children with metabolic diseases at Duke. Approximately 85% of children engraft and survive the transplant procedure. These children have normal cognitive development. Their vision is generally preserved and their hearts function normally. Children have a varying degree of orthopedic problems as they get older with some (approximately 50%) needing back or hip or knee or carpal tunnel surgery as they get older. With aggressive therapies and care, these children experience a very high quality of life. We expect their lifespan to be normal, but really don't know as children did not survive MPS before transplantation therapy."

According to Dr. Kurtzberg, there is a high probability that Gracie can have a long and happy life.

Gracie's Ready to Rumble

Sarah, Jimmy, and Gracie arrived today in Minneapolis and have the first meetings with doctors tomorrow AM. Please keep them in your thoughts. Sarah said Gracie is a great traveler and that she loved to fly. She was in a good mood and didn't fuss at all. Chris says it's because deep down inside, Gracie knows where she is going and is fully on board and ready to fight. We're ready in her corner....

In Chicago, we had some winter weather and my flight was canceled today. I hope to arrive tomorrow around noon.

Choosing Your Physicians

I hate to be a complainer, but I am fairly critical about many things. One pet peeve is clinician bad attitude, behavior, and bedside manner.

I love medicine. I'm a believer in science. I am astonished by the pace of change and rapid innovation in curing what previously seemed incurable. What folks in the medical profession accomplish day to day is remarkable, and I personally admire--and somewhat envy--the gifts they give to patients and families.

That said, nothing gets under my skin more than a callous, insensitive physician. I understand that they have personal lives and unique stressors, and they have bad days just like everyone else. However, I can't fathom the amount of stress they must be under to forget that a real human is awaiting your gospel - diagnosis, treatment options, timelines hanging by their fingernails every second that passes by. This is day to day for the doc, but life and death for the patient and family.

While Shands is a great regional health system, and serves the area well, it's clear to me why they aren't a national health care player. Based on my personal experiences with Shands back in the 1990s, as well as the experiences of the rest of my family, I'll probably never recommend or use them for any non-urgent care.

Granted, my exposure is limited, but it only takes a few bad impressions to drive someone away forever. Based on our experiences (these are gross generalizations. i have no doubt there are great physicians and great work at Shands, I've just not been lucky enough to find them):

• The physicians have horrible bedside manner
• The physicians are not accommodating, particularly regarding scheduling. Sarah's genetic counselor "couldn't fit her in" until March 18th. Ridiculous.
• The physicians are not proactive about presenting what cutting edge treatments are available, or where patients might find the information.

In fact, physicians at Shands, in my eyes, epitomize a couple of the problems in medicine today: First, the snail-like distribution of knowledge and new research findings. It should've taken those physicians a day or less to give a complete review of options and outcomes for Gracie.

Second, the physicians don't think that you know that you have a choice. They don’t think you’ll go see someone else. They don’t realize that they are running a business that requires attention to customer needs, and yes, customer service. There is no way Sarah and Gracie are going to wait six weeks to see that physician. Back in 1991, my physician at Shands didn't think that his horrible bedside manner would cause my dad to tell him where to stick it, driving us not only to another physician, but another hospital.

These people seem to be stuck in the world of Marcus Welby, where the physician is the owner of knowledge, and therefore the owner of the physician patient relationship. Those days are (or should be) over. Today, information abounds. We can all be informed, and we should turn the tables and choose our relationships and our physicians carefully.

The Mommy Speaks...

What does one say, do, feel when told that your daughter, your baby, your first child has a terminal disease? How do you keep moving when the world seems to spin out of control and your shoes are made of cement? How can you possibly believe that anyone in the world could have ever felt how you feel now or gone through such a terrifying ordeal? These are the things that whirl around in my head during my every waking moment and most of the moments that I should be sleeping.

Now I know the answer. You just do. You just go. You just move.

In my case, I was lucky enough to have a big push in the form of my 2 bossy, overeducated, and generally AMAZING older siblings. I know where to go, and I mostly know what to do. I have the opportunity to fight for my daughter's life and thats exactly what I intend to do. How fortunate am I to have a loving and supportive husband to join me in my efforts to thwart this enemy we call Hurlers. And with our army of family and friends we will go to the greatest of lengths for our Gracie.

Nothing about my journey with Gracie has been very easy, from conception it seems that we have dealt with one battle after another, but this bumpy journey has been filled with all the love and happiness that a mother could wish for. And as far as I am concerned, its not going to stop now.

With the help of the folks at the University of Minnesota, I intend to share a long lifetime of love and snuggles and smiles with my precious baby girl. My Gracie is a fighter, and so is her mom. So we will leave for the frozen north next week with fear, but mostly with hope that we can give our daughter the best life possible. That is what being a mother is all about.

How to: Making initial contact - sample

Here is a copy of my initial note to the research physician at the University of Minnesota. He called me within a few hours of sending it. Key points: keep it short, express admiration and interest in their work, create urgency, and include contact information.


Dear Dr. Orchard,

I hope this message finds you well, and thanks in advance for you time. My younger sibling, Sarah White, learned today that her 7 month old daughter has MPS-I. I'm writing to learn about the enrollment process for your clinical trial (NCT00176891), and collect any information I could pass along to my younger sister and her current physician.

Both myself and my other sibling (copied) have considerable experience in the health care industry, including some research experience. I'm familiar with the phenomenal outcomes for children with other genetic conditions (CF, in particular) following treatment at the University of Minnesota. We were excited to see your ongoing trial for MPS-I patients and would love to learn about your work in greater detail.

Best regards,

Mack Kelly

(Add Contact Info)