This is my favorite, but also my most painful gene : PYGM

Well, I think I can say that I am a pretty good geneticist, published at least 30 papers in internationally recognized journals that cover topics such as genetics of cancer, genetics of neurological diseases, genetics of stem cells and of embryonic development and a lot about the inherited susceptibility for diseases after environmental stress.

Now, in my early 50s, I have to anticipate that my own genome is also not free of any disease-predisposing abnormalities. I recognized some odd pain in my leg muscles about 10 years ago, when some really horribly pains struck me after walking down the stairway from our 5th floor apartment. 

After consulting various specialist doctors I ended up at the F.Miescher Clinic in Munich, which is specialize for neuro-muscular diseases. After taking a biopsy from my upper leg muscle they found that one enzyme, glycogene-phosphorylase V was completely absent. A subsequent genetic analysis that I did in our own lab confirmed that I am homozygous for a rare null-allele of the gene PYGM. McArdles disease, which is caused by this congenital condition, has a population frequency of 1 in 100.000. As in my case, both of my parents are heterozygous carriers (i.e. they carry one disease allele and one intact allele of PYGM, and due to the later they are both un-affected). I was the unlucky case of inheriting from both my mom and my dad their abnormal copy of PYGM. So I have the two bad copies in my germline, therefore I have the disease. 

O.k., I have to admit it is a disease one can live with quite easily.

There is

-  no life shortening associated

-  in my case, severe muscle pain only while climbing down (strange, I can climb up thousands of meters in the mountains, but not 10 meters downhill)

-  no problem riding the bicycle

-  no problem going dancing

-  no problem going skying (down-hill, long-distance, or touring)

When I walk down a long stairway, however, or if I climb down a hill, I got really bad muscle cramps which indicate severe destruction of muscle fibers (rhabdo-myelosis).

The only way to ease this pain in the past was to increase the glucose uptake before physical activity. But this was only partly efficient. No I got something new (and I have to admit that I found it through the internet at a patients forum:  It is a special kind of sugar (called D-Ribose, of which all our RNA molecules are made of), and it is prescribed against general muscles fatigue. The idea is, that D-Ribose can bridge the time between the depletion of glukose-generated ATP in the muscle cells and the production of new glucose from serum glycogen (which is impaired in McArdles patients) by quickly providing an energy source to the mitochondria.

I have to admit that I am not a very good biochemist, so I don't know exactly how and where D-Ribose can be used in  the mitochondrial cycle. Anyway, I believe that it works because it is based on scientific evidence.

From next week on, we will do our annual vacations in Bulgaria, and there are mountains of various levels of altitude, where I can do a controlled study with and without D-Ribose administration (because there is only a small market for D-Ribose, the stuff is about 50 x more expensive that ordinary sugar. So not really the stuff I will use to sweeten my tea with).

I will seriously report about it here. However will be the results:  These mountains are pretty impressive and beautiful anyway.  In the worst case, I will be caught on the very peak, and not being able to get home.  Than somebody has to come and catch me with a rescue helicopter.


Addenum: Maybe I should explain  why I nominated PYGM my most favorite gene: The germline mutation Arg50X (which causes expression of a truncated, inactive glycogen phosphorylase enzyme) not only predisposes strongly for McArdles disease with its sometimes painful muscles cramps, it has the beneficial side effect that the glukose level in blood serum is always quite low (because the muscle cells have to satisfy all their energy need from the free circulating glucose). This has the consequence that very little glucose is available to be converted in fatty acids and stored in the form of dad bod. So McArdle patients are usually pretty in shape, and even when they eat as much as they want, they have no problems keeping their body weight.