Spreading the Word

Two weeks ago I posted this after I sent an email to the Office for Rare Diseases Research in an attempt to get pancreatic agenesis onto their database. Overnight I received this reply from the lovely GARD people in the US:

The Office of Rare Diseases Research (ORDR) forwarded your e-mail regarding pancreatic agenesis to the Genetic and Rare Diseases Information Center (GARD). GARD is operated under the direction of the ORDR and the National Human Genome Research Institute (NHGRI) to help people find useful information about genetic and rare diseases. In your e-mail, you requested that we add pancreatic agenesis to our database to help people find information on this condition.

We appreciate your feedback, and we have added this condition to the ORDR list of rare diseases. We also created a Web page for pancreatic agenesis with information and links to resources. If you have any other suggestions or concerns, please contact us again.
http://rarediseases.info.nih.gov/GARD/Condition/10874/Pancreatic_agenesis.aspx

It's not the greatest scientific leap forward but hopefully by getting the information out there future parents and clinicians will be able to get answers easier than we did.

A Sensitive Little Man

For children born with no pancreas the first weeks and months are incredibly difficult. With each set of parents we ‘meet’ online the same story plays out. Very small babies, failing to thrive with wildly fluctuating blood sugars. Getting these babies to grow is key to their survival but as steady glucose levels are needed for good growth it’s a long, hard struggle to build up these exceptional babies.

 In our case we had the threat of an imminent heart operation added to the desperate need for him to gain weight as the stronger he was the better his chance of surviving surgery. In the end it was 5 months before he had to go under the knife but at the time we didn’t know how stable his heart would be.

The lack of glucose control is hardly surprising. Finlay weighed about 3 pounds when he was born and other children with his condition were similar sizes. Trying to be a substitute pancreas was always going to be difficult.

So I thought I’d go back and try to work out the scale of the task we were trying to overcome. Insulin Sensitivity Factor (ISF) is a measure of how much a unit of insulin will drop a diabetic’s glucose level. For rapid-acting insulin, such as Finlay is on, divide 100 by the total daily dose of insulin for the ISF in mmol/l, or divide 1800 by the total daily dose of insulin for the result in mg/dl. The examples given on this page have ISF values around 45mg/dl. Reading around the internet it seems values up to 200 are not uncommon for children.

So what was Finlay’s in the early days?

When he was first put on a pump he was given the Animas 1200, which at the time gave the smallest basal rate available of 0.025U/hr. During the early days he would be on this rate for most of the time, with the pump suspended when the BGL went below a set level. Over the course of a few days when he was 2-3 weeks old he averaged about 0.5 units per day (sometimes half that!).

So, 1800/0.5 = 3600mg/dl

1 unit of insulin would have dropped his blood glucose 3600 mg/dl !!!!!

Of course, 1 unit of insulin would comfortably have killed him and the ISF was completely irrelevant in those early stages as we were really just reacting to his sugars, chasing numbers, so it was never calculated or even mentioned. Even now we don’t use it. But it does illustrate the difficulties Finlay presented to the medical staff and us. And why his sugars swung so wildly. And what a great job everyone did to keep him healthy and get him to grow.

Now, 3.5 years later his ISF is around 200mg/dl. Still not easy to control but a hell of an improvement.

How Rare?

When people find out about Finlay's condition they often ask us how rare it is.
"How many are there in New Zealand?"
 "Er...him!"

Pancreatic agenesis is clearly a very rare disease. How rare is difficult to say. Children with this condition have neonatal diabetes. The rate for neonatal diabetes is estimated at 1 in every 400,000 to 500,000 live births, and pancreatic agenesis is a rare cause of neonatal diabetes. So putting a figure on it is very hard; 1 in 10 million? 1 in 100 million?

In the US there is the Genetic and Rare Diseases Information Center (GARD) which has a searchable database of thousands of rare diseases. Run by the Office of Rare Disease Research (ORDR), a branch of the NIH, it is the most comprehensive resource for rare disease research. What information do they have on pancreatic agenesis? Nothing. There's a couple of conditions where bits of the pancreas aren't present but nothing for patients missing the entire organ. So there's the answer. My son's condition is too rare for the rare diseases database!!

I started this blog in an attempt to get some information on the web about this condition so that other parents would have better luck getting answers than we did when our son was diagnosed. The GARD database is another potential source of information that any future parents could come across. So, with that in mind, I thought I'd see if I could get pancreatic agenesis onto the database. Earlier today I sent an email to the people at the ORDR: (sorry, a bit heavy on the science!)

Dear ORDR people,

I am the father of a 3 year old son with a rare condition called pancreatic agenesis. While searching your database I was unable to find an entry for this disease. The closest ones appear to be pancreatic beta cell agenesis and agenesis of the dorsal pancreas. Complete agenesis of the pancreas results in a life-threatening phenotype due to the complete loss of both endocrine and exocrine function.

Due to this severity, pancreatic agenesis was until fairly recently a fatal disorder, with patients succumbing during the neonatal period. The first report of long term survival appeared in 1980 but this remained the only case until the early 90s. Since the mid-90s survival has increased, however the total number of cases is very low (I suspect <100). A good review, although a few years old now, was published by Baumeister and colleagues.

There are two known genetic causes of pancreatic agenesis, homozygous (or compound heterozygous in one case) mutations in PDX1, which results in loss of the pancreas with no apparent associated anomalies, and homozygous mutations in PTF1A, which result in loss of pancreas and cerebellar agenesis which is sadly a fatal condition.

A third group exists, which includes my son, where pancreatic agenesis occurs with cardiac defects, for which the genetic etiology has not yet been published. This includes the proband from the Baumeister article referenced above. This group can also have a number of other associated anomalies including gall bladder agenesis, intestinal malrotation and developmental delay although the occurrence of these varies within the group.

With the rarity of this condition I found it very hard to get information following my son's diagnosis. An entry on your database may help future parents in their search for answers.

Many thanks for the work that you do.

Alan

It would be nice to get this condition recognised more widely. It may help parents trying to understand the condition but also might help medical staff diagnose a condition they are unlikely to have encountered previously and may never have heard of. As Finlay's neonatologist said when giving us the diagnosis, "Finlay is not on page 1 of the textbooks". I'll be interested to see if I get a reply.