Two doctor visits for Peter this week. We saw his endocrinologist on Wednesday. I asked her about Peter's dramatically reduced insulin needs during the past couple of months. She said that people often have a "honeymoon" period when the pancreatic cells that are still alive start producing some insulin again after being in diabetic "shock". Eventually they will be destroyed as the other ones were, and Peter's insulin requirements will go up again.
We've decided for the time being that we are not going to do anything about Peter's puberty. We are seeing a lot of startled looks when he tells people he's 16, but he really doesn't seem to notice. He isn't asking for his body to grow up. In fact, he seems to prefer that it doesn't.
Today we saw Peter's hematologist. We got permission from the hospital's God-knows-what committee so that they can draw blood at their lab and send it to various places for research use. So when we drew blood for routine tests today, we drew an extra tube for the researchers at Rockefeller University who run the IFAR. IFAR stands for "International Fanconi Anemia Registry". Peter probably doesn't have FA, but he fits the profile perfectly, and the IFAR people say that one negative chromosome breakage test isn't conclusive. They'll actually study all the genes that are known to be implicated in FA and see if any of his match. They'll also bank his DNA for future study.
I was hoping that we could draw blood today for the chromosome testing to see if Peter has DC (Dyskeratotis Congenita), but it didn't happen. DC is even rarer than FA, and Peter fits its profile pretty well too. After FA and DC, no other genetic bone marrow failure syndromes have been named (too few cases, not enough data), but there are clearly people who have a syndrome yet do not have FA or DC.
There seem to be two major ways in which these syndromes lead to bone marrow failure. In FA, there is a defect in the DNA's built-in repair mechanism. We all take "hits" to our DNA all the time, but it normally comes with the ability to mend itself. People with FA can't do that well. So the stem cells in the marrow gradually die away. If the person doesn't die from aplastic anemia, it's from cancer due to the underlying DNA repair problem. That's why people with FA who have successful bone marrow transplants still have a shortened lifespan. They eventually get tumors which are especially hard to treat. Chemo and radiation really do a number on cells. When the DNA can't repair itself ... well, you get the picture. (If there are any scientists among you, please forgive my ignorant and awkward attempt to describe something that I don't fully understand. I think I have the overall gist right. Please correct me if I don't.)
The chromosome breakage test for FA is pretty simple. There's a particular chemical that is very hard on DNA. If someone's blood is treated with that chemical and the chromosomes quickly break into pieces, that's FA. Of course, it's never as simple as that. There are not a small number of people with FA whose chromosome breakage tests are negative. Then there are people with positive chromosome breakage tests who never show the slightest sign of bone marrow failure. Many genes have now been implicated in FA, but genes don't work alone, and there are a dizzying number of possible combinations, not only within the identified group of genes but with others not yet identified. Compared with what we'll see in another 20 years, classification of these disorders is very rough right now.
People with DC have an entirely different problem. They have short telomeres. What I've been told is that the telomeres are like the little plastic bits at the end of your shoelaces that keep the strands from unraveling. When the telomeres are short, they don't work very well. As DNA replicates and replicates over the years of a person's life, more and more strands lose their telomeres and unravel. Once again, the stem cells in the marrow gradually die off.
There's a reason why it's the stem cells that die first. The blood-producing cells in the marrow are the most rapidly growing cells in the body. Compared with other cells, they have replicated millions more times. They really need robust DNA to keep on replicating normally. When there's an underlying defect, their engine starts to falter.
Because no two cases of genetic bone marrow failure seem to be exactly alike, there's just no way to predict what's going to happen to Peter. In the near future, some of his blood will be sent to a special lab in Vancouver by some researchers at the National Institutes of Health in Bethesda. There, his telomeres will be studied. What's interesting is that there are some people with very short telomeres who don't match any of the defective genes that have been implicated in DC. So it appears that DC may be the most common of a group of disorders all characterized by telomere dysfunction.
The people at Roosevelt should have genetic testing for FA done in a few weeks. They are a research lab, not a clinical lab, so those results are not "official". By law, they can't be reported to us, and they can't go into Peter's file. But our doctor can tell us about them. If we want them to be official, we have to have them repeated by a clinical lab. If Peter does have a defect that matches one of those known to be associated with FA, I'd certainly want to get that information into the record. Whether Public Aid will pay for it is another matter. They won't pay for the genetic testing for DC nor the way-out-there telomere study. Fortunately, the people at NIH will cover the latter.
Peter is at his most perky right now. His hemoglobin is higher than it's been in 3 years. He's actually riding his bike to school again! We can't predict what will happen next, but he could stay like this for a while. His counts will go down when he gets any kind of infection or suffers major stress. At some point it will be hard to keep him well because his infection-fighting ability won't be able to recover well enough. But that could be ... gosh ... even years in the future. It is also possible that Peter's marrow is having a "honeymoon" similar to his pancreatic cells' "honeymoon". It had to work very, very hard to keep his counts up during the months when his diabetes was getting out of hand -- and indeed, it didn't entirely succeed. So we may well see a dropoff over the next six months as the honeymoon ends.
Our hematologist says that bone marrow seems to have excess capacity allowing people with very little of it to remain healthy in some cases. The rule of thumb for normal marrow is that its cellularity should be 100 - the person's age. I'm 54, so my marrow should be around 46% cellular. Peter is 16, so his should be around 84% instead of the 5% measured last November. There are actually quite a things that can cause marrow cells to die off. Auto-immune processes, exposure to certain drugs or chemicals, radiation, chemotherapy, sometimes infections. When the problem isn't genetic, there is at least the possibility for the marrow to gradually recover its cellularity. But when the problem is right inside the cell, it will eventually hit a point where its DNA can no longer replicate and then it will die. One by one, his marrow cells will inevitably hit the wall.
But back to the happy stuff! Peter will really be able to enjoy SPICE this year, though his new Indian outfits may not fit. Unfortunately, he's gained back 15 pounds, and is looking much more corpulent again. If I ask him to try the outfits on, no matter whether he can get into them or not he'll have a big screaming meltdown, insisting that they do indeed fit. So I'm just going to bring them, along with his favorite two from last year, and we'll see what happens. The weight gain is one of only two elements of this story that are not "all good". His endocrinologist would like him to go on a more restricted diet but there is no way on earth for us to make that happen. Just now it was time for his bedtime snack and he wanted a peanut butter and jelly sandwich. Well, he took in plenty of calories all day, and he's only supposed to have a 15-carb snack. Not only that: the carbs in peanut butter are fairly low, but the FAT content and calories are high. I told him he could have half a sandwich, not a whole one. He immediately started to shriek. "LEAVE! ME! ALONE!" "It's MY body!" "You never let me do ANYTHING!" "I hate this family!" It went on for a good half hour, at high soprano and maximum decibels.
I know a few of my readers have kids with bipolar disorder, so they'll understand what I'm talking about. That's the other thing that's not all good. Peter has a lot more energy now to be ragingly bipolar. Things were a lot quieter for a while. That was nice.
