Myoadenylate deaminase deficiency
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Myoadenylate deaminase deficiency (MADD) is a recessive genetic metabolic disorder that affects approximately 1-2% of populations of European descent (making it a not particularly "rare" rare disease). It appears to be considerably rarer in Oriental populations.
Myoadenylate deaminase, also called AMP deaminase, is an enzyme that converts adenosine monophosphate (AMP) to inosine monophosphate (IMP), freeing an ammonia molecule in the process. It is a part of the metabolic process that converts sugar, fat, and protein into cellular energy. In order to use energy, a cell converts one of the above fuels into adenosine triphosphate (ATP) via the mitochondria. Cellular processes, especially muscles, then convert the ATP into adenosine diphosphate (ADP), freeing the energy to do work.
In some cases (such as greater than normal energy demand), other enzymes then convert two molecules of ADP into one ATP molecule and one AMP molecule, making more ATP available to supply energy. The resulting AMP molecule is not normally recycled directly, but is converted into IMP by myoadenylate deaminase. If myoadenylate deaminase is deficient, excess AMP builds up in the cell and is eventually transported by the blood to liver to be metabolized or to the kidneys to be excreted.
This failure to deaminate the AMP molecules has three major effects. First, significant amounts of AMP are lost from the cell and the body. Second, ammonia is not freed when the cell does work. Third, the level of IMP in the cell is not maintained.
The first effect -- the loss of AMP -- is mostly significant because AMP contains ribose, a sugar molecule that is also used to make DNA, RNA, and some enzymes. Though the body can manufacture some ribose and obtain more from RNA-rich sources such as beans and red meat, this loss of ribose due to MADD is sometimes sufficient to create a shortage in the body, resulting in symptoms of severe fatigue and muscle pain. This outcome is especially likely if the individual regularly exercises vigorously over a period of weeks or months.
The second effect, the absence of ammonia, is not well understood. It may result in a reduction of the amount of fumarate available to the citric acid cycle, and it may result in lower levels of nitric oxide (a vasodilator) in the body, reducing blood flow and oxygen intake during vigorous exercise.
The third effect, the reduction in IMP, is also not well understood. It may somehow result in a reduction in the amount of lactic acid produced by the muscles.
Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 50kg (100lb) of body weight per day.