Myoadenylate Deaminase Deficiency

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 [1] [2]. 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 [1] [3] [4]. Skeletal muscle pain (myalgia, which is sometimes be accompanied by cramping), frequent reports of fatigue, and weakness are the principal complaints [1] [3] [4] [5] [6]. 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 [4] [6]. The duration of symptoms is quite long before the diagnosis is made, as up to 10 years may pass before clinical suspicion is raised [1] [3] [4] [5] [6]. An atypical presentation of constant muscle pain without an exertional association has been noted in rare cases [6]. 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 [2]. Furthermore, other neuromuscular diseases may be concomitantly present [2] [3], 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 [3] [5]. 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 [1] [2] [5]. In this condition, the normal rise in lactate is typically not followed by elevations of ammonia [2]. To further solidify the diagnosis, a muscle biopsy that uses specific stains to determine enzymatic activity is recommended by some authors [2] [3] [4] [6]. As a definitive method, genetic studies that detect mutations in the MAD gene located on chromosome 1 may be employed [2] [3] [7].

1. Rannou F, Uguen A, Scotet V, et al. Diagnostic Algorithm for Glycogenoses and Myoadenylate Deaminase Deficiency Based on Exercise Testing Parameters: A Prospective Study. PLoS One. 2015;10(7):e0132972.
2. Tarnopolsky MA, Parise G, Gibala MJ, Graham TE, Rush JWE. Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans. J Physiol. 2001;533(Pt 3):881-889.
3. Teijeira S, San Millán B, Fernández JM, et al. Myoadenylate deaminase deficiency: clinico-pathological and molecular study of a series of 27 Spanish cases. Clin Neuropathol. 2009;28(2):136-142.
4. Abe M, Higuchi I, Morisaki H, Morisaki T, Osame M. Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient. Neuromuscul Disord. 2000;10(7):472-477.
5. Lim L, Palayer M, Bruneau A, et al. Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing. Ann Biol Clin (Paris). 2017;75(4):445-449.
6. Ahmed A, Lowden MR. Chronic Non-Exertional Myalgia and Myoadenylate Deaminase Deficiency: a Possible Association. J Clin Med Res. 2009;1(1):56-57.
7. Morisaki T, Gross M, Morisaki H, Pongratz D, Zöllner N, Holmes EW. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci U S A. 1992;89(14):6457-6461.

• Myoadenylate Deaminase Deficiency
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