Myoadenylate deaminase is the muscle-specific isoenzyme of AMP deaminase (EC 3.5.4.6). Deficiency of myoadenylate deaminase is heterogeneous in etiology and results in derangement of purine nucleotide catabolism and interconversion. More than 200 patients with this disorder have been reported, and reduced myoadenylate deaminase has been demonstrated in approximately 2 percent of muscle biopsy specimens submitted for pathologic examination for a wide array of indications.

Two distinct forms of myoadenylate deaminase deficiency are recognized. Inherited (primary) deficiency is either asymptomatic or associated with exercise-related cramps and myalgias. Acquired (secondary) deficiency is associated with a wide array of other neuromuscular or rheumatologic disorders. Because of the high frequency of one mutant myoadenylate deaminase allele, many patients with myopathy due to any of a variety of etiologies have a “coincidental” inherited deficiency of myoadenylate deaminase. In most patients with associated disorders, it is difficult to determine the contribution, if any, of the myoadenylate deaminase deficiency to the clinical phenotype. However, a coincidental inherited myoadenylate deaminase deficiency may be synergistic when associated with a second metabolic myopathy.

Recent evidence indicates that those individuals carrying at least one mutant myoadenylate deaminase allele have an improved clinical outcome should they develop congestive heart failure.

Inherited deficiency of myoadenylate deaminase is transmitted as an autosomal recessive trait. A single mutant allele harboring a nonsense mutation that results in the production of a severely truncated myoadenylate deaminase peptide is responsible for all cases of inherited myoadenylate deaminase deficiency characterized to date. The acquired disorder may result from a limitation in myoadenylate deaminase transcript availability, perhaps as a consequence of pathologic abnormalities caused by the associated disease. Genetic testing can be used to determine whether these latter individuals actually harbor a coincidental inherited myoadenylate deaminase deficiency.

Despite the relatively low incidence of the clinical phenotype associated with inherited deficiency of muscle AMP deaminase, the frequencies of the mutant allele are high, for example, 0.10 to 0.14 in several Caucasian sample populations.

When patients with myoadenylate deaminase deficiency exercise, their skeletal muscle does not accumulate NH3 and IMP, as occurs in normal subjects.

The myopathy in patients with inherited myoadenylate deaminase deficiency indicates that this enzyme and the purine nucleotide cycle, of which it is one component, play an important role in skeletal muscle metabolism during exercise.