I fully agree with that. I also think that we have to come to terms with the fact that much is not yet known and understood about those diseases. It is hard to do so when you have a physician who is very confident about what he/she thinks and not ready to admit the shortcomings of the knowledge in this field.

It is frustrating to think that you may have a treatable illness which is missed. But, I personally think that knowing the name of the illness doesn't make much difference if it doesn't lead to effective treatment.

For me, knowing the name of my illness didn't make much difference. What made a difference was understanding (at least partially) its mechanism and trying to tackle what is wrong and having a neurologist who doesn't have all the answers and was ready to be my partner (at least to some extent) in this quest.

Muscle contraction is a very complex process.

It requires input from the brain, which is transferred to the muscles via the NMJ. .

For most neurologists it stops there. That is why they go back and forth from brain scans to EMGs and all over again. Searching for the lost coin under the street lamp.

But, in reality this is only the beginning of a very complex process.

It requires that calcium will enter the cell, it then requires that calcium will be released from intra-cellular depots. It then requires that the mechanochemical proteins will work properly. For that to happen more than calcium is required, you also need other minerals and energy.

This energy is provided from fuels in our diet and is converted to ÄTP in the mitochondria. This process also produces reactive oxygen species which have a regulatory role (so too much or too little is not good). It also requires oxygen.

But, this is not enough, because this process has to be stopped in a timely manner, in order to allow proper relaxation of the muscle and preparation for the next contraction.

So many things can go wrong in this process.
It can be the result of genetic abnormalities in any one of numerous steps.
It can be the result of a genetic propensity which makes certain processes more vulnerable to exposure to certain toxins (which are unfortunately abundant in our environment).
It can be the result of antibodies directed against one of those proteins.
It can be a nutritional deficiency which leads to inefficient energy production or alterations in the normal regulatory process.
It can be an overshoot of an adaptive process.

You quite likely do not have any "classical" disease (I believe one of those would be found by now), so you have to find a physician who is ready to look for "rare zebras" and also be humble enough to admit what is not known yet.

I think you need to have functional tests which may help pin-point better where your problem is. I would consider having a full cardiorespiratory exercise test. For me this was the first "objective" test to show a significant physiological problem which could not be "in my head".

I recently came across a paper describing a rare genetic disorder, which effects both calcium signaling and mitochondrial function.

http://brain.oxfordjournals.org/cont....full.pdf+html

I am not suggesting that this what you have. It is just meant to show the complexity of neuromuscular diseases and how little is known and understood about them.

BTW-some patients with seronegative MG have antibodies directed against this protein, but most neurologists still think that this is not the cause of their illness. Therefore it is not checked routinely.

I am hopeful that within the next few years there will be a better understanding of those diseases, better diagnostic approaches and more effective treatments.