Meet Max, CblX...

In September 2011, Max's doctors took a blood sample from me and Steve.  That sample would be tested and DNA extracted to try to pinpoint exactly what Max's metabolic disease was.

One year later, we heard about that testing again.  Max was in the hospital after yet another intestinal surgery, and had a long recovery.  During that time, we met many times with his Metabolic doctors and talked quietly about their preliminary findings.  I spoke only briefly about it on Max's blog.  Only that we were hearing some interesting new things and would learn more as time went on.

This past year, we've certainly learned more about the findings, and today we can officially announce the name, and present the paper on Max's disease.

This article written on this new disease was released today, on The American Journal of Human Genetics, along with the CU Press release.  Max is Subject 1 in the article.  The disease was found in him first, then tested against other subjects to see if they also matched their findings.  This new disease is called Cobalamin X, or CblX.  I just typed CblC, which will be a habit I will have to break, as for nearly 10 years it's been what we knew Max to have.

It was Max's doctors and the researchers at the University of Colorado, School of Medicine, Human Genetics Lab who found this mutation.  They named it, along with collaborating labs around the world; including Max's research doctors at NIH, and the doctor in Canada which first got Max's biopsy at 4 months old to diagnose.  We thought it needed to have "Max" somewhere in the name, but as the gene is an X linked recessive inheritance disease, that's what they went with.  We'll, take it...it has a part of his name.

Their findings are so contrary to what we've always known Max's metabolic disease to be.  We were told when Max was diagnosed at 4 months old, he got two bad copies of genes from me and Steve, recessive genes we carried, which were made dominant in Max.  We were told he was missing essential enzymes in the processes of the cobalamin cycle which made his body build up deathly levels of acids. We were told he didn't have the gene mutation the other children with Cblc had, MMACHC.  

This lack of MMACHC gene is why they've kept looking all these years.  Which brought them to the discovery of Max's new disease, CblX.  

What they have found, Max has one bad gene called HCFC1.  Max has a normal MMACHC (CblC)  gene which theoretically would work normally. His HCFC1 X-linked defect causes a global disruption to the cobalamin pathway by not promoting MMACHC accurately.  This is what causes the build up of acids, not that he's missing enzymes in the Cobalamin pathway.  

If that sounds like a bunch of gibberish, it really boils down to this:  Max has one bad gene that flipped a switch in his metabolic process and turned some very important lights off, causing all his metabolic and neurological problems.  

We know now that the gene is not autosomal recessive (a bad gene from each parent), but is an X linked recessive inheritance disease.  I've written that twice now, so it must be important.  It is a bit, really. This is the first time in this type of metabolic disease where they are finding the diseases showing up from one parent, and in one case - from neither parent.  In Max's case, CblX was passed on from me, to him. 

Go back to 9th grade Biology with me for a minute.  Girls have 2 X chromosomes, boys have an X and a Y.  When the mother has 2 X's, and one of those X's is bad, she has another one to cancel the bad one out.  Her son does not have an extra X to cancel out the bad.  In my DNA, that one gene, the HCFC1, is bad...corrupt...flawed.  When I passed my DNA on to Max, it copied that bad HCFC1 gene, and wham - gave him CblX.  If my baby had been a girl, she would not have CblX.

Once we realized the genetic defect did not come from Steve, we started barking up my family tree and had my parents and siblings tested.  None of them had the same gene mutation, which mean it started de novo, or spontaneously in me.  This simply does not happen in these types of metabolic diseases, Organic Acidemias.  It is a first time finding, and one that is really important in the world of genetics.  It's one big fat, "who knows why this happened; but it did", and the result is Max's disease. 

What does all of this mean?  Nothing, and everything.  

It's like when Max was born, we were given a huge box of puzzle pieces and knew we were only looking for one puzzle piece.  We've found that puzzle piece, so now we can start putting the puzzle together.  Treatment will not change in Max.  We still have no prognosis, as he's the first one (and oldest they know of) with the disease.  Now that this is common knowledge, we hope we can find the other boys.  Yes, it's a "boys only" club.  So, in Max, not a lot is changing.  Just the four letters after his name; CblX.

For Children's Hospital Colorado, and University of Colorado School of Medicine, plus the collaborating labs around the world who worked on finding this gene and naming the disease, it changes everything they've known up to this point about this type of disease.  It changes the way they look at the cobalamin diseases, and also what this HCFC1 gene does.   It will mean more research; years and years of research.  It means Max has played a very important role in changing science.  In that regard, it's a pretty big deal.  And one we, as a family, are happy to be a part of.  Every parent wishes for their child to one day make a huge contribution to society, and the world.  Max has done that by simply being his amazing self, and his unique make-up is changing the way scientists and doctors will look at how these diseases work.

We've been digesting this information for a while now, so I don't want to regurgitate it all out at once here.  We will be discussing it more, and more as we get more information to share.  But the long and the short of it is, this is Max, CblX.