The Nitty Gritty of the Test Results

We met with the Metabolic Geneticist regarding Ryan's test results and what to do next.  I think I've already mentioned to you that he is a walking database of pure genius.  I brought all of his notes and drawings home with me so that hopefully I can relay at least most of what he taught me.  I'm sure I'll miss some of it.

Talking with him is like attending a 400 level college class about a subject that you're really, really interested in learning everything about when you're really only ready for the 100 level class.  I want desperately to grasp everything he says.  I study before I go and prepare for the appointment.  I ask good questions, take good notes, and still I leave wishing I understood more.  I guess I just wish I could spend more time being taught by him.

Anyway ... let's get to the nitty gritty.

So, you probably already know that Ryan was tested for all kinds of things because he had lost a bunch of his skills.  Most of them came back negative.  However, at the end of November, the DNA test for Niemann-Pick Disease Type C found  him to be positive for 1 gene mutation.  "At least a heterozygote for NPC."  There needs to be 2 gene mutations to be diagnosed with the disease.  The 2nd gene mutation was "questionable."

Interesting to me, maybe to some of you all also, maybe meaningless to the medical team though, was that there were variants of unknown significance on his DNA diagnostic testing.  Seven (to be exact) were listed.  Since most of you probably won't have a need to see DNA testing, they list the Nucleotide Change, the Amino Acid Change, the Location, the Lygosity, and then a Reference(s)/Comment(s).  Kind of cool, right?  It's amazing what all they can tell about a person's body now.  This is off the current test results topic, but I will want to discuss this with the doc at the next appointment.  It should be a good lesson.  I can only imagine how much I will learn.

Anyway ... back to the topic... so from that test we knew for sure that Ryan had 1 gene mutation for NPC and a questionable 2nd.  So, it was recommended that we do "biochemical testing."

The biochemical testing consisted of a skin biopsy, which we did in early December.  With the skin biopsy they are then able to grow the cells (fibroblasts) in the lab and look at their ability to transport and store cholesterol.

So, here's where it gets interesting again ... and confusing ...

The transport of cholesterol in the cells is studied by measuring conversion of the cholesterol from one form to another ("esterification").  If we were to look at only this test result, we are back to a POSITIVE test result.   However, the storage of cholesterol is assessed by staining the cells with a chemical ("filipin") that glows under ultraviolet light. This can show whether the cholesterol is being stored inappropriately in lysosomes, the recycling centers of the cell. The filipin staining was NEGATIVE.

So we have 1 + gene mutation, 1 ?? mutation.  1 negative test result and 1 positive test result.  What does that equal?  Well, it does not = Niemann-Pick Type C Disease.

This is where we get to the real nitty gritty stuff...

Instead the doctor says we then have to go back in the process to say, what affects cholesterol uptake?  Why would his be so low if he doesn't have NPC?  There could be Mitochondrial Issues.  There could be Copper Metabolism issues.  There could also be several other issues that "we don't even have human models for yet."

So what does that mean?

Well, first let me say, I'm surprised you're still reading this ... Mitochondrial ... and Copper ... both of these require that we do a muscle biopsy.  We're doing that in less than 8 hours.  So, check.  If the muscle biopsy points us in the direction of Copper, then we may have to do a liver biopsy.  Yuck.  But, we'll deal with that if and when, not tonight.  As for the other issues that "we don't even have human models for yet,"  he's going to research them.  They do have "animal models" for some of the issues.  I guess we'll learn more about those things if we need to.  Maybe some day there will be a mother blogging about her child being diagnosed with the RyMann Syndrome. Has a nice ring, right?  Hmmm... not a bad thing as long as we find a cure, too.

The muscle biopsy will be done tomorrow.  Information from it will come back in stages, but all of the information should be back in 4 weeks.  I'm off to get some sleep now.  I just wanted to share all of this before I forgot it all.

PS   If any of my doctor friends are reading this and I made any mistakes, please feel free to correct me.  ;)