A run for anyone's money!

Since Finlay's birth we have been helped by so many wonderful people. The debt we owe is larger than we could ever pay back. But that shouldn't stop us trying. I posted previously about how we were able to raise funds for one of the charities that helped us through a photo competition that was won by a photo featuring a 5 month old Finlay. (I say we helped but it was really our friend Simon who took the photo and did the work.)

Well we're raising more funds for the @Heart charity and this time it's Vicky that's doing the hard yards....15 long kilometres of them!

The City2Surf is an annual charity run in Christchurch that gives her the chance to raise lots more money to help families of children with heart defects. And this morning she got a piece in the local paper

Finlay's Latest Sports Gear?

An insulin pump is not an everyday item for most people so quite often we'll get questions about what the little device with the tube attached to Finlay is. Sometimes they'll guess that it's medical, other times they'll come up with some stranger conclusions, quite often they'll think it's an MP3 player. We're getting used to the horrified stares from concerned people thinking what dreadful parents we are letting such a young child damage his ears listening to music! Usually a brief explanation allays their fears. Today was a new one for me though...

The New Zealand National Road Cycling Championships were being held close to where we live this weekend so we popped along to see the best cyclists in the country compete against each other. There was quite a crowd near the top of the hill section of the race enjoying the atmosphere and the glorious summer weather.

There were lots of very fit-looking lycra-clad spectators with all the latest high performance gadgets. Another family was watching beside us and the father noticed the pump Back Buddy on my three year old and the tube coming out of it and asked me, "Is that a mini Camelbak?" (For those not obsessed with sport a Camelbak is a backpack containing a bladder and drinking tube that can be filled with water for running, cycling or walking)

"Sorry?" I said, not quite sure of what I'd heard.

"Is that a Camelbak?"

Partly taken aback and partly amused I replied, "Yeah, I forced him to run up the hill to get here," quickly adding "no, it's an insulin pump. He's diabetic"

"Oh right"

At this point his embarrassed wife slaps his arm in admonishment, not quite believing what her husband had just said.

I think she was relieved to see a grin on my face and I explained that it was often confused for other things like MP3 players. But this was a new one for us.

Finlay and his brothers make some noise as the cyclists tackle the climb

Finlay's Fantastic Fluorescent Frogs

Until recently we've been hooking Finlay's insulin pump onto the top of his pants. This has been a little difficult with him being so thin and the pump being so heavy. The best solution was a pair of rather stylish braces.

But as he is growing up situations change. The old solutions become the new problems.

Braces are very practical and occasionally can be very stylish (especially ones with dinosaurs on!) but when it comes to toilet training they become a bit of a nuisance. Teaching a child the basics of toileting is always a challenge but throw in unclipping of braces, making sure the pump stays out of the toilet, watching where the tubing goes, it all becomes a bit fraught.

So thanks to a mother's suggestion on a forum we have taken delivery of this neat backpack with fetching fluorescent frog styling via the Diabetes Mall that will hold his pump and keep it away from any risky ablution-associated dangers.

Finlay sporting his frog covered backpack as he searches for pirates through his makeshift telescope

So far it seems to work pretty well. He is able to drop his pants at will..... hopefully only when necessary, but boys will be boys! We have managed to avoid having to fish the pump out of the toilet bowl, Finlay seems to like it and the other kids at preschool seem to just accept it.

Unfortunately with his infusion sites still in his thigh we've had a site ripped out following an over-eager pant-dropping but this is a learning process and he'll figure out the intricacies in his own time.

 Looking pleased with his new gear

Why?

One question that has been niggling at me since Finlay was born is simply, why?

I think this is a common question for parents of children with chronic conditions. Why? What went wrong? Did we do something wrong? In many cases it can all be mixed up with feelings of guilt or anger or both.

For me it was more of a simple why. Finlay had a genetic abnormality. We weren’t to blame. There was nobody for us to blame. It simply was. Our genes mutate between every generation. Sometimes it makes no difference, sometimes it might be advantageous, and sometimes, like with us, it could be pretty devastating. Mother Nature plays to her own rules. She is often beautiful and awe-inspiring. Occasionally she sucks!

So I have never felt guilt or anger. Frustration, yes, oh yes!! But anger, no.

But the one question that wouldn’t go away was why? A genetic mutation, but which gene? What could lead to such devastating abnormalities?

Well, two causes of absent pancreas were known. Recessive mutations in the Pdx1 or Ptf1a genes had been shown to cause pancreatic agenesis. In these cases each parent had a bad copy of the gene and when the child inherited both bad copies, the pancreas didn’t grow. But for Pdx1 mutations there was usually a family history of diabetes which we didn’t have, and those cases were only missing the pancreas, not the gall bladder and had no problems with the heart or any other organ. For the Ptf1a cases they also had cerebellar agenesis, meaning they were missing a large part of their brain, sadly a fatal condition. Neither of these genes seemed plausible for Finlay.

So, I looked for other cases. I searched out every case I could find in the literature, downloading papers or writing to clinicians in far-flung corners of the world to ask for reprints. I found about 30 cases of pancreatic agenesis. Some dead, some alive. A few with a known cause, most without. One thing I noticed was that about a third of the cases also had cardiac defects. Could they all have the same cause?

The other thing I noticed was that many of the cases were from consanguineous parents, i.e. the parents were related, quite often cousins, as is common in a number of cultures. The relevance of this is that if a mutated copy of a gene exists within a family, there is a far higher chance of two people from that family passing on two mutated copies to their children than if the parents are unrelated.

What struck me was that none of the cases with cardiac defects appeared to have related parents. If these cases were caused by the presence of two mutated copies of the same gene it could be expected that at least some of the cases would be from related parents due to the increased chance of passing on two mutated copies. But the absence of related parents suggested that these cases were caused by a single non-inherited mutation, a mutation present only in the child with the disease, not the parents.

But still, which gene? Sadly, this is about as far as I got. I considered lots of genes and came up with some possibilities, but there are over 20,000 genes in a human cell. A real needle in a haystack.

Fortunately, our DNA, along with Finlay’s had been sent to the Peninsula Medical School in Exeter, England. This is where the experts in monogenic diabetes are. And they had a cohort of samples from children just like Finlay. And they had some amazing pieces of technology. What they did next was they took our DNA and that of another child with no pancreas and cardiac defects and his parents and they sequenced our genes, all of them! They sequenced the genetic code of every single one of the 20,000+ genes in our cells, over 30 million pieces of genetic code from each one of us. Then they filtered through them looking for differences.

Since the mapping of the human genome a decade ago we have had a consensus sequence for what the genetic code of a human is. And each one of us has a slightly different version of this code. When they looked through Finlay’s genes they found over 23,000 differences, single letter changes or small deletions or additions to the code.

As this condition is rare they were expecting the mutations involved to be new to science. So the next thing they did was take out all the differences that had already been found in other humans using huge databases of genetic variation. Then they excluded all the ones that weren’t in coding parts of the genes, i.e. that weren’t involved in the sequence of the gene products or that didn’t change the gene product (protein). Next, because they were looking for a non-inherited mutation they removed any differences that were found in either parent.

After all this they were left with one single mutation.

Once they had done the same with the other child’s DNA they were also left with one single mutation. A different mutation… but in the same gene!

It seemed that one gene was the cause of the disease in both children.

Then they went back to the rest of their pancreatic agenesis cases and sequenced just this single gene. Of the 27 children in their cohort 15 had mutations in this gene, and all but one of those cases had cardiac defects. And in all the cases for which DNA from both parents was available the mutation was not found in either parent: it was a non-inherited mutation.

This Sunday past these clever people at Exeter published their findings online in the journal Nature Genetics adding another gene, GATA6, to the list of causes of monogenic diabetes. Science has an important addition to the understanding of how the pancreas develops.

Like many scientific advances, this finding asks as many questions as it answers; what is the mechanism that causes Finlay’s problems? Why is there so much variation in the symptoms of these children: some have no gall bladder, some have liver problems, some have developmental delay, some are prone to seizures.

Perhaps one day we’ll figure these out. But for now I have my answer.

Despite Everything

Recently a few diabetes bloggers I've been reading have posted pictures and videos of what their kids do despite diabetes, to show that these are just normal kids doing normal things. The pick of them was Reuben's chicken catching.

Now Finlay probably couldn't catch a chicken. Heck, I probably couldn't catch a chicken! But he can catch balls. This video was taken just before bedtime recently so excuse the pump weighing down his PJs!

In this blog I highlight many of the challenges that we have to deal with every day with our son's disease. It would be easy to be negative and focus on the downside all the time. Although there is nothing amazing about this video, the sight of Finlay laughing hysterically shows he is too busy enjoying life to let his condition get him down. So we shouldn't either!

The Coolest Toy in the Playground

As he grows up Finlay will have to deal with many things resulting from his condition, particularly when getting on with other children. Today we got a glimpse of the future, albeit a very cute one!

Another child at his preschool was being collected at the end of the day. He turned to his mummy and said,

" I want one of those" pointing to Finlay's pump.

"Ah, no. You can't get one of those" replied his mum.

"But... Finlay's got one!!...."

I hope their ride home wasn't too bad, with a 3yo tantrum from being denied the 'toy'.

Digesting the Problem

With such a unique disease we have some unique challenges to deal with. For the last week we’ve been struggling with a new problem:

First a little background. In addition to diabetes, not having a pancreas means Finlay can’t produce the enzymes he needs to digest his food. We have to give him his enzymes with each meal. During the day we use Creon, small spheres of enzyme that we mix with his food. At night, when we feed him through his gastrostomy tube straight into his stomach we use Pancrex, a powdered form of enzymes that we dissolve in water and pass through his tube.

This has been working pretty well and has helped us keep his blood sugars steady(ish) and him as healthy as possible.

But now that has all changed. Pancrex, the drug we rely on for him to digest his feeds at night, has been discontinued.

So how can we give him enzymes during the night? The only drug available to us is the Creon that he takes orally during the day.

Option 1: Wake him up and give him some Creon capsules.
This worked the first night. We woke him up and he sleepily did as he was told, opened up and swallowed the enzymes mixed with some apple puree.  The poor wee man didn’t know what was going on. By the next night he had worked out this was going to be a regular occurrence and he wasn’t happy. Tired, angry, crying and in no mood to start eating anything. A ten minute struggle to get him to eventually swallow his food was enough to convince us this was not a long term solution.

Option 2: Pushing the small spheres through his gastrostomy tube.

 Our dietitian found a research paper that suggested we could mix the spheres in thickened water and push them through the tube. The photo shows our result. The spheres just clumped together at the end of the tube. Assuming this was the spheres not getting through the valve at the start of his gastrostomy button we put on an unblocked tube and flushed with water. But the water wouldn’t budge. It turned out some spheres had got through the valve and become blocked in the gastrostomy button, the bit of tubing that sits in his abdomen wall linking the feeding tube to his stomach. I had no option but to change the gastrostomy. Luckily with all the fuss, he had woken up so I took out the button,  got him to place some cloth over the opening to stop his stomach contents spilling out onto the bed (which is quite impressive for a tired, sleepy 3yo), and quickly got his spare gastrostomy out of the box, lubricated it and squeezed it through the hole into his stomach and inflated the balloon with water to hold it in place. Not a successful evening!!

Option 3: Crush the spheres with a mortar and pestle, mix them with water and stick them down the tube.

This sounds simple enough but here we were outdone by the clever people who designed the spheres. The enzymes are contained in these little spheres which are all crammed into a capsule. When the capsule is swallowed it dissolves in the acid of the stomach releasing the spheres. Now this is the clever bit. The spheres have an enteric coating that protects the enzymes through the stomach acid, then when they are passed into the duodenum (into where the pancreas would normally release the enzymes), the alkaline environment dissolves the enteric coating allowing the enzymes to digest the food, mimicking closely what would happen in a normal person.

But when you crush these spheres, the enteric coating becomes separated from the enzymes. Then when you add water and try pushing through the gastrostomy, the coating from hundreds of little spheres all coagulates together and forms a thick blockage in the tube. Failed again!

Some of the enteric coating after I picked it out of the end of tube with a needle

Knowing that the enteric coating dissolves in alkali we unblocked the feeding tube by passing some dissolved baking soda through the tube but this was another frustrating evening.

Option 4: So after many emails between us, the hospital, the pharmacist, and apparently other hospitals in both New Zealand and Australia we think we have a solution. We are crushing the spheres in bicarbonate (baking soda) to dissolve the coating then passing through his tube, flushing with plenty of water. It seems to be working. So far.

Another unique week of unique challenges for a unique child.