Myoadenylate deaminase deficiency

Myoadenylate deaminase deficiency (MADD) isrecessive genetic metabolic disorder that affects approximately 1-2%populationsEuropean descent (making itnot particularly "rare" rare disease). It appearsbe considerably rarerOriental populations.

Myoadenylate deaminase, also called AMP deaminase,an enzyme that converts adenosine monophosphate (AMP)inosine monophosphate (IMP), freeing an ammonia molecule inprocess. It ispart ofmetabolic process that converts sugar, fat,protein into cellular energy. In orderuse energy,cell converts one ofabove fuels into adenosine triphosphate (ATP) viamitochondria. Cellular processes, especially muscles, then convertATP into adenosine diphosphate (ADP), freeingenergydo work.

In some cases (such as greater than normal energy demand), other enzymes then convert two moleculesADP into one ATP moleculeone AMP molecule, making more ATP availablesupply energy. The resulting AMP moleculenot normally recycled directly, butconverted into IMP by myoadenylate deaminase. If myoadenylate deaminasedeficient, excess AMP builds up incellis eventually transported bybloodliverbe metabolized or tokidneysbe excreted.

This failuredeaminateAMP molecules has three major effects. First, significant amountsAMPlost fromcell andbody. Second, ammonianot freed whencell does work. Third,levelIMP incellnot maintained.

The first effect --lossAMP --mostly significant because AMP contains ribose,sugar molecule thatalso usedmake DNA, RNA,some enzymes. Thoughbody can manufacture some riboseobtain more from RNA-rich sources such as beansred meat, this lossribose dueMADDsometimes sufficientcreateshortage inbody, resultingsymptomssevere fatiguemuscle pain. This outcomeespecially likely ifindividual regularly exercises vigorously overperiodweeks or months.

The second effect,absenceammonia,not well understood. It may result inreduction ofamountfumarate available tocitric acid cycle,it may resultlower levelsnitric oxide (a vasodilator) inbody, reducing blood flowoxygen intake during vigorous exercise.

The third effect,reductionIMP,also not well understood. It may somehow result inreduction inamountlactic acid produced bymuscles.

Symptomatic relief fromeffectsMADD may sometimes be achieved by administering ribose orally atdoseapproximately 10 grams per 50kg (100lb)body weight per day.