Pyruvate Dehydrogenase Complex Deficiency

Edit:
I want to start out this post with an update.  Further down you will see me write proudly about our decision not to vaccinate. Everything about the decision was wrong, from my reasoning to the results. My intentions were well-placed, but we know where intentions can lead. The last five years has been a complicated journey, a road where I have grown and learned a lot.  Two years ago our decision not to vaccinate put Brianna in a frightening and vulnerable position and we saw her suffer a lot from my mistaken reasoning. Fortunately, she did not lose her life, but she could have, and children with her disorder have from the flu. But it put into stark relief how much we had at stake. She and our other two older children are now caught up on all their vaccinations - it took about 18 months and nary a reaction other than screams of protest, even from Brianna, the child most likely to and vulnerable to a reaction. Our fourth child is now vaccinated on schedule.



The day has come. We have finally received the "official" diagnosis for Brianna. Last Monday we were called in to meet with the genetics/metabolic nurse to receive the news that we suspected, but was now confirmed. They got back the skin biopsy and the blood test that confirmed that Brianna has Pyruvate Dehyrogenase Complex Deficiency (PDCD).

PDCD is a very rare disorder. Most people have never heard of it (I sure hadn't!). There's a few hundred cases across the country. Rather than try to explain it, here is a link to the National Institute of Health's rare disease database explanation of PDCD.

Brianna has the mutation on the E1 alpha gene. We don't know if it's a new mutation in her, or if she inherited it from me. They drew blood from me last week and sent it off for genetic testing. If I am a carrier, since it is X-linked, that means that every child will have a 50% chance of inheriting the gene.

So there's a lot going on in our heads right now. It's hard to find a positive in finding out that your child has a progressive metabolic disorder. To know that there is no cure or "fix" and that in time, things will get worse. There's no way to know if it will be 1 year or 30 years.

There are good things though. Brianna is doing very well despite her disorder. The metabolic nurse that works with us says that in 18 years she has seen 6 cases of PDCD, and Brianna is the least severe that she has seen. There are 5 other cases currently on the island (4 of those are treated at Kapiolani, the local hospital, not Tripler where we are seen, the military hospital), and Brianna has the least severe presentation of those cases. So there is a lot to be thankful for. She is still making progress in her development. With the new medications, we've seen a lot of progress in her energy level, and her seizures are rare now that she is on anti-seizure medications.

The disease progresses the most slowly when healthy. Sickness is what speeds progression. We are so grateful that she has such a strong immune system. I thank God that we were led on a path that has helped make her so strong. If we had made different choices, I think that she would have been in a much worse state right now. She breastfed for over two years - the first nine months was exclusive. After that it was just limited solid food. She didn't have any formula until after her feeding tube was put in, and she was 16 months old at the time. And now I am able to continue pumping milk to give her several ounces a day. There is so much immune system-building properties to breastmilk, I really believe that this is an enormous reason why she is so healthy. If I had listened to the doctors and nutritionists who encouraged me to back off breastfeeding and supplement, well, let's just say that I am very happy that I listened to my gut.

She has also never had a vaccination. I know this is a hot topic, but we made the choice not to vaccinate. One of the biggest reasons is because we believe that God created our bodies to work a certain way. I truly believe that vaccinations interfere with the immunological responses of our bodies (well, I don't believe that, I know that because that's the point of vaccinations). While the principle is great, I think that the immune system is overloaded by the massive amounts of vaccinations that are given the first few months and years of our children's lives. And for some children, that overload causes serious damage. And there's no way to know if a child will be more susceptible to that. Look at Brianna. There was no obvious reason not to vaccinate, except for our philosophical and religious beliefs. Although she was small, she was deemed healthy, and no one implied otherwise for the first five months of her life. We didn't know that she had a serious health condition. A condition that puts her at risk for vaccination reactions. Reactions that could very well have resulted in her getting lactic acidosis, and since they had no idea what was wrong with her - it most likely would have resulted in a massive decline, and very possibly death.

I'm so grateful that my big sister paved the path for me, and caused me to think about a lot of the parenting decisions we have made. I really believe that if it weren't for her, we might have made different choices, and blindly listened to her doctors without realizing the implications - even the "minor" ones at that point, that our daughter might not be with us today. Thank you, Heather. You have no idea how much you've helped us walk this path.

So there is so much to be thankful for. We could look at this as something devastating, and let it cripple us. We could rage and curse and turn our backs on God because he "allowed" this to happen to us. Do I cry out to God? Do I ask Him why us? I absolutely do. But I look at Job, and I remember God's response to him. Basically, to remember who he is talking to. God sees the bigger picture. We don't know what is going on behind the scenes. I know that this is not something God is doing to us. It just IS. Pain is a part of life. Part of being in a sinful world.

I look at Brianna, and instead of seeing a tragedy, I choose to see a miracle. She is an amazing and special little girl. One who has overcome incredible odds and continues to surprise and delight us. She has a smile that will melt any heart. She is our Holland.

WELCOME TO HOLLAND
by
Emily Perl Kingsley.

c1987 by Emily Perl Kingsley. All rights reserved

I am often asked to describe the experience of raising a child with a disability - to try to help people who have not shared that unique experience to understand it, to imagine how it would feel. It's like this......

When you're going to have a baby, it's like planning a fabulous vacation trip - to Italy . You buy a bunch of guide books and make your wonderful plans. The Coliseum. The Michelangelo David. The gondolas in Venice . You may learn some handy phrases in Italian. It's all very exciting.

After months of eager anticipation, the day finally arrives. You pack your bags and off you go. Several hours later, the plane lands. The stewardess comes in and says, "Welcome to Holland ."

" Holland ?!?" you say. "What do you mean Holland ?? I signed up for Italy ! I'm supposed to be in Italy . All my life I've dreamed of going to Italy ."

But there's been a change in the flight plan. They've landed in Holland and there you must stay.

The important thing is that they haven't taken you to a horrible, disgusting, filthy place, full of pestilence, famine and disease. It's just a different place.

So you must go out and buy new guide books. And you must learn a whole new language. And you will meet a whole new group of people you would never have met.

It's just a different place. It's slower-paced than Italy , less flashy than Italy . But after you've been there for a while and you catch your breath, you look around.... and you begin to notice that Holland has windmills....and Holland has tulips. Holland even has Rembrandts.

But everyone you know is busy coming and going from Italy ... and they're all bragging about what a wonderful time they had there. And for the rest of your life, you will say "Yes, that's where I was supposed to go. That's what I had planned."

And the pain of that will never, ever, ever, ever go away... because the loss of that dream is a very very significant loss.

But... if you spend your life mourning the fact that you didn't get to Italy , you may never be free to enjoy the very special, the very lovely things ... about Holland .

Seizures

For a while, part of our morning routine has been to deal with Brianna's seizures. I would take her out of the crib, lay her on the changing table, and she would have a seizure.



They used to be infrequent, but in the last few months (since returning from the mainland) they have been increasing in frequency, to the point that she was having them every morning, and sometimes multiple times a day. We tried changing up what we did in the morning, but she'd just have the seizure somewhere else.














The first seizure I noticed was a year ago, while at my sister's house. I told the neurologist about it, and they scheduled us for an EEG. The EEG was a big fat failure. I don't know how they expect these things to work. We came in at the middle of the day, theoretically when she'd be ready for a nap. I was supposed to get her to sleep, lay her down, and then they'd hook her up to the electrodes on her head. Well, I nursed her to sleep and layed her down on the very uncomfortable bed in the sterile room that had no personality to it at all. Sure enough, as soon as he started hooking her up, she woke up. Nothing would get her back to sleep. I have no idea how they ever do a successful EEG with a younger child or baby. So then they did an EEG while she was sedated. And all that told us was that she didn't have a seizure while sedated. For the next year, I'd bring up the seizures at the appointments. I was either told the EEGs didn't show anything, or just kind of brushed off. The "episodes" were very infrequent at that point, so I didn't press it (stupid me). After we returned and they came up more frequently, I brought it up again, but the neurologist just said he didn't think they were seizures. Finally, I was able to get some on video. Thank goodness...as soon as he saw the video, he affirmed that it was a partial complex seizure. We talked about different medications and settled on Kepplar. Only one year wasted...

She was still having seizures, though not as frequent, for the last two weeks (she's been on the medication for two weeks), so yesterday the neurologist had me increase the dosage. She didn't have a seizure this morning, so we'll see how well it works.

Yet another example of the frustration I have about getting the point across about what she needs.

You'd think that these doctors would learn that I've NEVER been wrong when something's going on with her. I'm so frustrated and so sick of being brushed off. It takes so long to get anything done. Referrals end up taking at least a month until we get to an appointment, usually like two or three.

I'm hoping if the seizures go away, especially if she's having them while sleeping, she'll find more energy during the day. Despite sleeping for 10 hours at night and typically taking 1-2 hour nap she still seems very tired all day long, with brief spurts of energy. Here's hoping.

Nephrologist

We had an appointment with the nephrologist last week. I was more than a little concerned when I got the call on Thursday to set up the appointment. I had to ask her what a nephrologist was! When she said kidneys, I began to get concerned that something was up with her kidneys. But I set it aside until today, figuring if it were major, we wouldn't be waiting five days for an appointment (I would hope!)

I totally had forgotten that she had gotten a referral way back last June. In her urine test her calcium levels had come up high. Which is something linked to kidney stones. We had gotten an ultrasound of her kidneys at the time and I never heard anything more of it.

The appointment today was related to that test. Her calcium urate (sp?) levels were 2.0, the high end of normal is 0.6, so it's definately high. Too much calcium gathers up in crystals and so on and so forth. It's not dangerous, but it can increase the likelihood of UTIs, kidney stones, etc. No fun to have a 5 year old with a kidney stone, I'm thinking.

This most likely has nothing to do with her condition. It looks like it's a genetic thing. My husband had his first kidney stone at 20, which is very uncommon, and his grandfather had a lot of problems with stones. So we're going to get some more urine tests on Brianna, and do yearly renal ultrasounds to make sure all is well. And we're getting a test for Garin as well, just to see if it's affecting him.

My Enigma

I've decided to start a separate blog for Brianna's journey. It has been such a rough 2 1/2 years for our family. She's such a precious light, and I didn't want to bring down our family blog by focusing on the medical "stuff" which gets so overwhelming sometimes.

Our journey with Brianna started just over 2 1/2 years ago. The first sign of a problem was when I went in for my 34 week appointment. The midwife was concerned when I measured 5-6 weeks behind. Previously, I'd been measuring about 1-2 weeks behind, but nothing majorly concerning. She did a fluid check and my fluid levels were fine. The next week I started my bi-weekly NST (non-stress tests) and weekly fluid level checks. They also did the initial growth scan. They would need two (two weeks apart) to see if she was no longer growing. In her initial growth scan she measured at about 30 weeks gestation - we were 35 weeks along. I realize now that I just stopped getting bigger at some point. All of the following pictures were taken around 36 weeks of pregnancy. You should be able to tell which one was Brianna.





We never made it to the next scan, because she was born the next Saturday. Her birth extremely quick, but uneventful (well, I barely made it to labor and delivery, she was born less than 8 minutes after pulling into the parking lot, but there were no medical events to note during her birth). She scored normal on her apgar - 8, and was able to nurse immediately with no apparent problems.

Soon, however, I started noticing...irregularities. She passed one small bowel movement during our 48 hour stay. No one made any note of this (she really should have had at least 2 bowel movements while we were there). And I was concerned that she wasn't really nursing very well. The LC came in and said not to worry, it was normal for babies to be uninterested in nursing the second day because they were so tired. She said that since I had successfully breastfed one child, that I shouldn't have any problems. We went home, she seemed to nurse fine, we changed plenty of wet diapers...but no messy diapers. After 9 days of no diapers, I called the pediatric hotline. I was told it was normal, and nothing to worry about. So I stopped worrying. How I wish I hadn't...

See, all of these were early signs of a problem. Things that really don't seem a big deal to most people, but since Brianna was technically premature, I really feel that there should have been more concern about following her progress. But there wasn't. And so for the next 4 months, nothing happened. Two week appointment, three month appointment, given a clean bill of health. Despite my expressing concern that she seemed a little bit behind (she was a little slow on smiling and cooing and laughing). And of course she didn't hold her head up at all.

Brianna had very poor muscle tone, couldn't hold her head up, yet they didn't express concern. Looking back, I really should have been more aware of her not hitting milestones. But I assumed that she was just behind because she was a preemie, and she would eventually catch up. After all, that's what everyone told me. Watching Liam now, I realize how much I missed with Brianna. I do take responsibility that I just never noticed. She was so quiet, she barely moved, she didn't really observe what was going on around her, and you really had to work hard to get her to smile. You can see in this picture that she made no ability to hold her body. She was only 4 days old, but I realize now most babies make some effort to move their bodies around.


Here she is at two months old, and looking now, I realize how unusual it is for a two month old to just lay there.


And you can see her here doing tummy time at 3 1/2 months old. Not even able to pick up her head. Liam, a month younger (so 2 1/2 months, her adjusted age), was able to roll from tummy to back, and could lift his head up 90 degrees and started to push himself up. Brianna could barely lift her head off the ground for a second.

Around this time we started to realize there was something going on with her head shape. It seemed kind of bulgy in the back, and really flat on the sides. I'd found online that it was common with preemies, but it had to do with laying on their sides in the NICU. Brianna was never in the NICU. So I had a few questions to bring up at her 4 month appointment (which would actually be closer to 5 months, because we were a few weeks behind on her appointments).

Here she is at 4 1/2 months



And here's a picture we took to take note of her head shape



At her five month appointment , we started to get some concern expressed by medical personnel. Her pediatrician expressed concern about her slow growth. At her 3 month appointment she was 9lbs 8oz and 22.5 inches. Which was pretty good considering she was born 4lb 12.5 oz and 17.5 inches and left the hospital at 4lb 9oz. So in her first three months she gained five pounds and grew five inches, which is pretty gosh-darn good. However, from 3 to 5 months she only went up to 10lb 10oz and 23.5 inches. So just over a pound in two months...which is NOT good. The doctor also expressed concern about her physical delays and her muscle tone. And of course, the thing that we took the biggest note of was her head shape, the doctor mentioned craniosynostosis and referred us to the neurosurgeon. From there, things started happening. Nine days later we met with the surgeons, and they scheduled us for surgery five days later.

HERE is a link to the post about her surgery. It occurred on February 3rd.

A month later, on March 11th, we began the quest to figure out what was causing Brianna's delays. At this point I really believed that she was just behind, and that she would catch up. I don't think it really occurred to me that something BIGGER was going on. We met with the developmental pediatrician at this time and it began to sink in.

As the weeks went by, we had more appointments . None really seemed to answer any questions. Including one very frustrating appointment with a pediatrician who claimed that her problems were because she just wasn't getting enough milk from me because I wasn't making enough milk. He told me a metabolic disorder was highly unlikely. Oh how I'd like to see that man again and let him know how wrong he was. You can see by reading the post I linked earlier in this paragraph that I was beginning to see that there was something more going on. Re-reading that post, I see that in the almost two years that have gone by, it really doesn't seem that much has happened to answer my questions, and I'm constantly asking the same things over and over.

In April of 2009 we started to address her feeding issue. I reread my blog entry that detailed how we began her entry into eating solid foods. This is an ongoing challenge for us. She still is only able to mostly handle purees, and the consistency is a very important factor. Just tonight she gagged and threw up on a homemade puree of lamb, rice powder, butternut squash and apple because the texture was too thick. She does try to feed herself certain things, but she tends to mostly just let them dissolve in her mouth before swallowing. She doesn't know how to chew. And she doesn't know how to suck on a sippy cup or straw, except by accident. Which makes the prospect of weaning her off the feeding tube unlikely at this point.

Seizures. I first mentioned seizures in December of 2009. Over a year ago. I mentioned them again and again. We did an EEG, which was an utter fail. I don't see how they expect any child that age to successfully go to sleep in a small, uncomfortable room, and THEN stay asleep while the dude puts a bunch of electrodes all over their head. Does anyone think this out? FAIL. And then they did an EEG while she was sedated for her MRI. Nothing happened - shocking. So that was it, drop the subject, end of story. Except these "episodes" I keep seeing more and more frequently. Brushed off by the neurologist. Finally I get some on video (thank you droid phone) and show the neurologist. Lo and behold, yep, she's having seizures. She's been on the meds for a week and a half. I'll be calling him tomorrow, because I don't see that they're working.

We've had SO many diagnoses thrown about. Cerebral palsy has apparently been ruled out. They're still working through the mitochondrial testing. We traveled to Rainbow Babies in August to have a muscle biopsy taken. She doesn't appear to have an obvious mitochondrial disorder. But certainly SOMETHING is amiss with her muscle/cellular energy cycle. Most tests have come back normal, but there are a few that are slightly high or slightly low, or just barely in the range of normal. It just seems so weird that so many things are slightly off. One of the disorders they're looking into is Pyruvate Dehydrogenase Complex deficiency . The metabolic professional here seems to be leaning in that direction, but reading the report from Rainbow Babies I get the impression that she doesn't seem to quite fit that diagnosis. Which is fine with me, because the prognosis is very poor for children with that disorder. There are a few other disorders being thrown about that I haven't heard one way or another.

So that's where we stand right now, as far as diagnosis. About where we stood a year ago. Big fat question mark. So now, we ask again: where do we go from here?