Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle.

Abstract

Abstract. To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD).' 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 1 1). The MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content ofmuscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content ofmuscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for by the combined increases of adenosine, inosine, hypoxanthine, and IMP. Studies performed in vitro with muscle samples from seven MDD and seven non-MDD subjects demonstrated that ATP catabolism was associated with a fivefold greater increase in IMP in non-MDD muscle. There were significant increases in AMP and ADP content ofthe muscle from MDD patients following ATP catabolism in vitro, while there was no detectable increase in AMP or ADP in non-MDD muscle. Adenosine content of MDD muscle increased following ATP catabolism, but there was no detectable increase in adenosine content of non-MDD muscle following ATP catabolism in vitro.These studies demonstrate that AMP deaminase deficiency leads to reduced entry of adenine nucleotides into the purine nucleotide cycle during exercise. We postulate that the resultant disruption ofthe purine nucleotide

Myoadenylate deaminase deficiency and forearm ischemic exercise testing

“…Sabina et a1 observed delayed ATP regeneration after exercise in MADA-deficient subjects compared with that in normal subjects (5,20). In the absence of MADA activity, AMP is not converted to IMP.…”

“…It was also possible, however, that adenosine concentrations might increase in those subjects, but this was not observed. One possibility is that adenosine is produced when MADA activity is absent, but is retained intracellularly ; however, this was not observed in the muscle biopsy specimens studied 'by Sabina et a1 (20). Alternatively, adenosine might be released, but be taken up by endothelial cells, causing vasodilation (23).…”

Can Genetics Predict Sports Injury? The Association of the Genes GDF5, AMPD1, COL5A1 and IGF2 on Soccer Player Injury Occurrence

“…The study involved 289 male soccer players (aged [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

Progressive myalgias and polyarthralgias in a patient with myoadenylate deaminase deficiency

“…More than 40 cases of MADA deficiency have now been described, and the major functional and metabolic abnormalities associated with this disorder have been summarized (6). About two-thirds of the reported patients with MADA deficiency have manifested a symptom complex consisting of postexertional myalgias, cramping, or weakness, and generalized fatigue.…”