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.