For reasons that are not understood, many people with defective variants of the AMPD genes are asymptomatic, while others have symptoms including exercise intolerance, and/or muscle pain and cramping. ;Fatigue * MADD lowers aerobic power output, so increased anaerobic power is needed to perform the same amount of work. * Without myoadenlyate deaminase, heavy activity causes<unk>  to be released into the cell or perfused into the surrounding tissues. Fatigue and sedation after heavy exertion can be caused by excess<unk>  in the cells which signals muscle fiber to feel fatigued. In the brain, excess<unk>  decreases alertness and causes sleepiness. In this way,<unk>  may play a role in fatigue from MADD. * Recovery from over-exertion can be hours, days or even months. In cases of rhabdomyolysis, which is the rapid breakdown of muscle fibers, time to recovery is dependent on duration and intensity of original activity plus any excess activity during the recovery period. ;Muscle pain * Muscle pain from MADD is not well understood, but is partially due to high levels of lactate. Increased levels of free<unk>  temporarily decrease pain, allowing over-exertion without awareness. The over exertion can cause mild to severe cases of rhabdomyolysis, which is painful. *<unk>  mediates pain through<unk>  receptors. MADD causes an increase of free<unk>  during heavy activity which may cause exercise-induced muscle pain. Over time, excess free<unk>  down-regulates primary A1<unk>  receptors, leading to increased muscle pain. Secondary receptors (A3) increase peripheral inflammation, which also increases pain. ;Muscle cramping * The cause of cramping is unknown, but may be related to elevated lactate, increased calcium signaling across the sarcoplasmic reticulum caused by membrane instability from reduced levels of ATP, or increased levels of free<unk> . ;Muscle weakness * Muscle weakness is not a major symptom, though the progressive effects of chronic muscle damage from rhabdomyolysis will eventually cause significant weakness. Similarly, the long-term metabolic effects may result in nerve damage. Potential complications There is an increased risk that statin (cholesterol-reducing drugs) will cause myopathy (muscle weakness) in individuals with MADD. Anesthesia has the potential to cause malignant hyperthermia, an uncontrolled increase in body temperature, and permanent muscle damage in patients with MADD. Individuals with MADD are advised to notify their anesthesiologist about their condition prior to surgery. In most cases where myopathy is present with MADD, a second muscle disease is present and symptoms are worse than either disease in isolation.
Adenosine monophosphate deaminase deficiency type 1
Adenosine deaminase 2 deficiency
Adenosine deaminase deficiency
Galactose-1-phosphate uridylyltransferase deficiency
3-Methylcrotonyl-CoA carboxylase deficiency
Ornithine aminotransferase deficiency
Ribose-5-phosphate isomerase deficiency
Adenine phosphoribosyltransferase deficiency