Myoadenylate deaminase deficiency is one of the most common metabolic disorders of the skeletal muscles and is characterized by mutations in genes responsible for the production of this enzyme. The predominant symptoms are myalgia, predisposition to fatigue and exercise intolerance, as well as muscle cramping that can last for years before the condition is recognized. Although a clinical diagnosis can be made based on findings obtained during history taking and the physical examination, biochemical tests, muscle biopsy, and genetic studies are necessary for confirmation.
The clinical presentation of myoadenylate deaminase deficiency stems from the absence of the enzyme that facilitates the conversion of adenosine monophosphate (AMP) to inosine monophosphate (IMP) and ammonia (NH3) as a byproduct  . As this process plays an important role in the generation of energy, the vast majority of patients reports symptoms that are related to exercise and physical activity   . Skeletal muscle pain (myalgia, which is sometimes be accompanied by cramping), frequent reports of fatigue, and weakness are the principal complaints     . Virtually any skeletal muscle can be affected - the facial muscles, the upper and lower extremities, or even a generalized presentation may be seen, and atrophy might also be reported  . The duration of symptoms is quite long before the diagnosis is made, as up to 10 years may pass before clinical suspicion is raised     . An atypical presentation of constant muscle pain without an exertional association has been noted in rare cases . The prevalence of myoadenylate deaminase deficiency is high: between 1-2% of the population is established to suffer from mutations that produce this effect. The deficiency shows an autosomal recessive pattern of inheritance with a very broad phenotypic range . Furthermore, other neuromuscular diseases may be concomitantly present  , which is why the diagnosis of myoadenylate deaminase deficiency may not be easy to make.
The diagnostic workup of myoadenylate deaminase deficiency should start with a thorough patient history that will reveal the symptoms and their duration, as well as onset and progression. Clinical suspicion can be raised when an association is made between exercise and the appearance of complaints, in which case a more detailed approach should be sought. Elevation of creatine kinase (CK) is nonspecific, but very frequently found in this patient population  . One of the key laboratory tests that point to a deficiency of myoadenylate deaminase is the evaluation of lactate, pyruvate, and ammonia levels 10 minutes after resting from physical activity   . In this condition, the normal rise in lactate is typically not followed by elevations of ammonia . To further solidify the diagnosis, a muscle biopsy that uses specific stains to determine enzymatic activity is recommended by some authors    . As a definitive method, genetic studies that detect mutations in the MAD gene located on chromosome 1 may be employed   .