McArdle's Syndrome is a glycogen storage disease (Type V, for those counting), so it's a problem with our savings account. These patients are allergic to exercise which makes this the dream disease of nerds everywhere (McArdle even sounds like a good nerd name, doesn't it?). People with McArdle's syndrome are lacking the muscle form of glycogen phosphorylase, so they are unable to convert stored glycogen (savings) back into glucose (checking) to use in glycolysis (ATM). So when they begin exercising, their muscles use up the available glucose, and then are left with no fuel source, which understandably causes some problems (in this case muscle cramps). Luckily for the lives of those with McArdle's, the liver version of phosphorylase is still active, so these patients can still convert glycogen stored in the liver to glucose, and get the necessary energy to all cells, but in strenuous exercise the liver just can't keep up with the muscle.
Those who can't convert the liver glycogen into free glucose get the much worse.....
von Gierke's Disease
Patients with von Gierke's are missing glucose 6-phosphatase, which is a key enzyme in turning liver based glycogen into free glucose. So these patients can accumulate money in their savings account, but never take it back out again- trust fund! Kinda. This is a major problem, because once the free glucose from meal has been used up, the patient's body has no energy source to turn to. This can cause severe hypoglycemia (low blood sugar) with even short lengths of fasting, such as the time between normal meals. Patients present in infancy with massive enlargement of the liver (because of glycogen buildup), hypoglycemia, acidosis (low blood pH) and growth failure. The disease is relatively easy to control in adults by frequent ingestion of corn starch which is slowly digested to provide a continuous source of glucose. However infants usually require a 24-7 nasogastric feeding tube until they are old enough to be persuaded to eat cornstarch all day.
But of course glycogen metabolism isn't the only process that can have problems....
Beriberi
I love tropical diseases. They have such fantastic names, which means they are about the only diseases I remember over long periods of time. Beriberi is a severe thiamine (vitamin B1) deficiency. It is a tropical disease because thiamine isn't that rare of a vitamin, so severe deficiency usually only occurs in populations that rely entirely on polished rice for food. Thiamine deficiency in the developed world occurs in alcoholics who are mostly relying on alcohol for their caloric intake. It is given the much more dull name of Wernicke-Korsakoff syndrome, or as I like to call it, AlkyBeriberi.
Thiamine is necessary for the TCA cycle, which we haven't talked about yet. The TCA cycle is like glycolysis, in that it produces ATP (cash). It actually takes glycolysis byproducts, and further extracts ATP from them, but requires other inputs as well, such as oxygen. The TCA cycle, though, is much more efficient than glycolysis, and actually provides the majority of our ATP.
So people with Beriberi have a severe lack of energy supply in their cells, which means that their bodies' systems begin to gradually shut down. The nervous system is the first affected because the brain is much more dependent on glycolysis and the TCA cycle for energy. Other tissues are also capable of using fats and proteins through other pathways. So patients exhibit mental confusion, unsteady gait/lack of motor control, vomiting, and coma. Those with Wernicke-Korsakoff also sometimes exhibit a strange type of congestive heart failure that is characterized by high cardiac output.
Also interestingly, Arsenic and Mercury poisoning disables the same enzyme that is disabled in Beriberi, leading to similar mental/neurological problems. This is the origin of the phrase "Mad as a Hatter", because hat makers used mercury nitrate in their hat making processes, frequently succumbing to mercury poisoning.
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