HELP! 2yo with hypotonia

My daughter is 32 months old and we are trying to understand where her test results and symptoms are leading us.

Her symptoms include: areflexia of both upper and lower extremities, significant global hypotonia, UE, LE and trunk weakness (ability to sustain muscle activation is poor also),a mild intention tremor (ataxia), a muscle biopsy showing fiber type-1 predominance, brain MRI showing "minimal increased T2 signal identified within the periatrial white matter likely representative of under-myelination rather than gliosis", Sensory Integrative Dysfunction (severe tactile defensiveness,vestibular processing difficulties,delayed equilibrium responses and deficits in bilateral integration), a severe speech delay,moderate gross motor delay,possibly dysmorphic features (including a rare tooth anomaly), a high arched palate,and an unusual, sweet, pungent body odor (urine diabetes screen came back normal).

With all of this, she is doing remarkably well! She is walking, even running in her own way (does show some right sided weakness though), has been able to hop for the first time since we got her orthotics and is beginning to make some real progress with her speech.

My concerns are trying to understand what the under-myelination in the brain means and how it might relate to the lack of DTRs.  I have the MRI report but won't be able to speak to the neuro for another month about what we are doing next (any ideas on what our next tests should be?). Is there any chance, considering the gains she has made, that we could be dealing with some sort of leukodystrophy? Any idea on how the abnormal muscle biopsy might play a role in all of this? Until the MRI they were thinking a congenital myopathy but I'm assuming that's not a likely candidate anymore. Are there any myelin disorders which are not at least slowly progressive? And finally, any idea what they mean when they say "under-myelination (de- or hypo-myelination?)?

Any help with any of this would be greatly appreciated. I just want to try to prepare for what the possibilities are and what questions I need to ask at our next neuro visit.

Thanks,
Kass

P.S. one other item from the MRI that I am wondering about... it says "Flow void is noted within the major intracranial vessels." Does this mean anything?

[CCF Neuro[P] MD, RPS]

Dear Kass:

I am sorry to hear about your little girl.  Without having examined your child, seen the films and the laboratory work up thus far, it is difficult to tell you what your daughter has.  If the MRI showed hypomyelination that would mean that the brain hasn't myelinated as much as a normal brain.  A demyelination of the brain would mean that the myelination process was once normal but something has happened and now there is less myelin and hence a demyelinating process.  

There are a few muscle disorders that give you a dominance of fiber types.  The congenital variety is fiber-type disproportion myopathy.  There is a predominance of type I fibers, which are 15% smaller than type II fibers.  The EMG (has she had one?) showes a neuropathic process.  These children have varying degrees of dysmorphic features, and joint contractures.  Proximal weakness is greater than distal.  There is facial weakness, high arched palate, ptosis, and disturbances of ocular motility may be present.  However, intellectual processes are usually normal.  

In many of the leukodystrophies usually have an elevated CSF protein.  Was a CSF analysis performed.  Some mitochondrial disorders have a picture of hypomyelination both peripheral and central, but here the labs are usually abnormal.  Since the labs must have all been normal or you would have mentioned something, I am not sure about the diagnosis of mitochondrial disease.

So, if not already done I would get urine organic acids (sent to Dr. Richard Kelly at Kennedy-Krieger, serum and urine amino acid screen, carnitine and acyl carnitines in both serum and urine, EMG study, CSF analysis.  Those tests that have been performed already I wouldn't repeat.  

Since I did not see the MRI it is difficult to tell you what the neuroradiologist meant.  It might be due to volume averaging, or it might be an area where blood isn't flowing properly, or it might be an artifact.

Sorry I couldn't help you more.

Sincerely,

CCF Neuro MD

[kass]

Thank you so much for your response.

She actually has not had an EMG yet, nor has the CSF or any other labs been done so far.  They have only done the CPK(normal), a choromosome study(normal), and a urine diabete's screen(normal).  We are going to see a new ped next week that has a background in endocronology, who is preparing to do the blood work that hasn't been done yet.  I'll be sure to take this response with me so we can be sure to look for everything that you mentioned.  Unfortunatly, the neuro and my regular ped, have been bouncing us back and forth as far as more blod work and I finally got fed up and found someone to help us.  There hasn't even been a general blood work up done on her thus far.  We are fixing all of that.

Really appreciate also your comments on the "flow void" comment.  We'll see what the neuro has to say about it on the 21st.

Thank you so much, you have helped more than you can know.

Sincerely,
Kass

[CCF Neuro[P] MD, RPS]

Dear Kass,

You are very welcome. Let us know about the visit and what is brought up.

Sincerely,

CCF Neuro MD

[kass]

Sorry to post again, but I failed to mention some things in my original post.

The last six weeks we have been seeing a progressive lethargy in our little girl. She has always been a more sedentary child, but would play while sitting down. Now she is more often than not, laying down, sucking her thumb, not playing at all. I had tried to not worry about this because our ped didn't seem to be, but the last week and a half, it's become noticably worse. She is now not even enticed by being at our friends homes with other kids and toys she loves around, and others are starting to notice how run down she is. There has been no signs of illness during this six weeks.

We also observed this weekend that, while walking and running she is using her left leg oddly (it appears to just be weaker), she is toeing in in her shoes or curling her toes on the left foot and walking on the outside of the foot when walking (while still rolling in if standing still). We checked for injuries and in doing so, realized that her left calf is noticably smaller than her right. It is atleast 1/4 inch smaller. I have never noticed this before, and feel that I would have if this was not something new (atleast something that finally progressed to a point of noticing). The only ouchy she says she has is on the outside of the foot thats bearing all the weight when she is walking...nothing on the area thats being kept from touching the ground.

Not sure if this new information modifies the testing you suggested, but wanted to ask and find out. I am very concerned about these developments, mainly whether this could be a sign of progression.

Sincerely,
Kass

[CCF Neuro[P] MD, RPS]

Dear Kass:

I would let your pediatric neurologist know about what your describing.  From a distance it is impossible to tell you what is going on.  There are just to many things that can give the picture that you describe.

Sincerely,

CCF Neuro MD