Posted by ccf neuro M.D.* on September 13, 1997 at 19:47:05:

In Reply to: Undiagnosed 4-1/2 yr old boy - any ideas? posted by Terri Mason on September 10, 1997 at 14:24:58:

I am desperately trying to find somebody who can either point me in a new
direction or who has a child or patient with similar neurological symptoms.
Here's the quick run down:

First symptom was ocular nystagmus at age 1-1/2. No other neurological or
opthamological symptoms at this time. MRI done and was negative for any
abnormalities.

Second symptom was optic nerve atrophy which presented about 6 months
later and continued to worsen over the next year. Optic nerves have
remained stable for the past 1-1/2 years. Visual acuity currently
measured at 20/200.

Growth stopped for a period of 1-1/2 years from age 2 - 3-1/2. From birth
to age 2, he was on 90th percentile growth curve, by the age of 3-1/2,
had dropped to 5th percentile line. Growth resumed and has been stable
along the 35th percentile for the last year. Another MRI done at age 3.
Radiologist noted that optic chiasm was slightly small (neurologist
disagreed) but everything else appeared normal. Both MRIs were done with
contrast.

At age 3, neurologist noted an end-tremor which still exists(he is now 4
years 10 months old).

Age age 3-1/2, neurologist noted "jumpy reflexes" which are still present.

At age 4-1/2 (4 months ago)he has lost the ability to control the right
side of his face. Neurologist has ruled out Bell's Palsy and believes
it is due to either a small stroke or a problem with the 7th cranial
nerve. The right eye is also open much wider than the left eye. The
condition has not improved since it started and did not follow an illness.

At age 2 developmental delay began showing up, especially in the area of
motor development. Fine and gross motor skills estimated to be at the 2 -
3 year old level. The way he walks and runs, although functional, are
very odd and uncoordinated looking. He walks and runs with a visible foot
drop. He still can't stand on one foot or hop with both feet simultaneously
and he loses his balance often when engaging in more active play. His
hearing is normal.

Visual Specialists who work with him say that his vision is not having an
impact on the way he moves. Although he is beginning to hold a pen or
pencil with a more adult-like grasp he is still unable to reproduce
anything more complex than a circle or two intersecting lines.
Intelligence is average.

Recently we have started noticing what appear to be involuntary "jerky"
movements but don't happen often enough (maybe once a day) to be certain
that they are involuntary.

His grandmother recently observed him watching television and his leg was
bouncing up and down very fast. She asked him what he was doing with his
leg, he replied "Nothing." She asked him to stop it and he said "I can't
stop it, it just does that." We haven't observed that since but it was
only about a week ago.

Also over the last two weeks he has started having more "accidents".
Although he wasn't perfectly potty trained, he would only have an accident
maybe once every two weeks - and then it was for an obvious reason. For
the last two weeks he has been having an accident at least once a day and
yesterday, twice. He doesn't wet the bed and he hasn't had any problems
with bowel movements, just urinating. He appears to be waiting too long
and by the time he makes it to the bathroom he isn't able to hold it long
enough to get his pants down. I'm not sure if this is relevant or not,
but since it's new, I thought I would mention it.

My son's primary care physician, pediatric-opthamologist, pediatric
neuro-opthamologist and pediatric neurologist all have no idea what is
going on. The latest guess is some sort of mitochondrial disease but
they can't find one that he fits into. His primary care physician thinks
that there is no way he has a mitochondrial disease because of the
extremely slow addition of new symptoms and the fact that although he
is developing very slowly, he does continue to develop. Since his teacher
brought up the mitochondrial disease issue I have researched them
extensively and must agree that if it is a mitochondrial disease, it's one
that hasn't yet been documented and one that is extremely slow in it's
progression.

Has anybody ever seen anything like this? How common is it for
neurological problems like this to go undiagnosed? Does anybody have
a wild guess? I'm not expecting a diagnosis from anybody here, just
looking for a new direction that somebody might be able to point me in.

Any suggestions or information would be greatly appreciated and if you've
read this entire message - thank you for your interest.

Sincerely,

Terri Mason
tmason@artisoft.com
--------------------------------------------------------------------------------------------------------------------
Terri,

First let me express my understanding of what a difficult ordeal this must be for your son, yourself, and family, and how not knowing WHAT it is that is doing this to your son must make a difficult situation even more unbearable. In reviewing the very nice historical summary you have provided, I think that many of your son's clinical symptoms suggest a problem with his mitochondria; he sounds like a super sped up version of a mitochondrial disorder called Leber's hereditary optic neuropathy. There are a number of other congenital nutritional disorders/enzyme or vitamin deficiencies (B12, vitamin E or one of their transporter proteins can cause symptoms similar to this but usually in adults) that might cause similar symptoms, although it is likely that these have already been investigated by your pediatric neurologist. There is a test known as MITOCHONDRIAL DNA ANALYSIS that is the definitive be-all and end-all test for mitochondrial dosorders, including ones that do not officially exist or follow artificial rules and definitions that us doctor's use in an effort to compartmentalize and categorize diseases. I think there's only one or two labs in the country that do it, and proper specimen collection is essential. If abnormal, this would at lkeast tentatively give you a diagnosis, even if an unusual or perhaps new one. It is also important to find out if possible the exact cause of the symptoms if the cause is genetic, for purposes of genetic counseling and assessing what if any risk subsequent children of yours, should you choose to have them, might have. Mitochondrial disorders are unusual in that only a mother can pass along such disorders, whereas other metabolic inherited diseases may be maternal or paternal or both in origin. In any case as complex as your son's, a second (and even third) opinion may prove fruitful, as many inherited disorders are very rare and clinical experience with them limited; thus what one doctor, no matter how smart or well trained, may have never seen a case of, another doctor may have seen a case or several cases of that might "remind" them of the diagnosis.

We do have a pediatric neurologist, Dr. Bruce Cohen, at the Cleveland Clinic who has a specific interest in the diagnosis and treatment of mitochondrial disorders, and also has considerable interest in nutritional disorders, and he would be a GREAT person for a second opinion if you're interested in getting one and travelling to Cleveland is practical for you. Our number is 1-800-223-2273; ask for PEDIATRIC neurology appointments if you are interested.

We wish you well in dealing with the challenges that your son faces, and hope that you find this information useful in some way. As always, actual diagnosis and treatment of your (son's) medical condition should be strictly in conjunction with your treating physicians, as information provided in the neurology forum is intended for general medical informational purposes only.