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Plasma adenosine, inosine and hypoxanthine concentrations were assayed in seven control subjects, five myoadenylate deaminase deficient (MADD) patients and six McArdle patients before and after ischaemic forearm exercise. The plasma adenosine increase was very low in all test groups and there were no significant differences. The MADD patients showed a significantly lower increase of plasma inosine and hypoxanthine after exercise as compared with the controls. In the McArdle patients the increase in plasma inosine and hypoxanthine after exercise did not differ significantly from the values measured in the controls. The ischaemic exercise test with measurement of plasma inosine and hypoxanthine might be of diagnostic value in MADD, but not in McArdle's disease.

Subjects with myopathies associated with certain enzyme defects often show abnormal concentrations of lactate (LA) and ammonia (NH3) in blood after ischemic exercise. Myoadenylate deaminase (MAD) deficient patients produce only small amounts of NH3, whereas LA rises to normal levels. On the other hand, patients with certain enzyme deficiencies in the glyco(geno)lytic pathway show the opposite. However, the concentrations in blood are dependent on the exercise performed. Standardization of tests for screening purposes, therefore, is necessary. For ischemic contractions, experiments were performed to find the optimal combination for force and frequency, using the highest LA and NH3 concentrations in blood as criteria. Eleven healthy subjects performed ischemic isometric contractions with a handgrip dynamometer at frequencies of 30 and 50/min(-1) and force levels of 50%, 65%, and 80% of maximal voluntary contraction (MVC). A combination of 30/min(-1) and 80% MVC was found to give the best results.

Muscle biopsies were taken from 10 control subjects and five AMP deaminase (AMPD) deficient individuals before and after an ischaemic isometric exercise test and analysed for purine nucleotide, NAD+, creatine phosphate (CP) and lactate content. The decrease of ATP induced by the exercise test was significantly lower in the AMPD deficient patients than in the controls, but the decrease of creatine phosphate and the increase of lactate did not differ. There were no significant differences in the exertional performance level between patients and controls and no evidence was obtained of an increased energy expenditure per unit of performance in AMPD deficiency. The AMPD deficient individuals were equally capable of maintaining a high adenylate energy charge (EC) as the control subjects, which indicates a normal regulation of the balance between ATP consumption and ATP regeneration. ATP, ADP and total adenine nucleotide (TAN) but not AMP, were significantly elevated in the AMPD deficient patients as compared with the controls before as well as after the exercise test. This underlines the role of AMPD activity in the adenine nucleotide catabolism of skeletal muscle.

An ischemic forearm test with simultaneous measurement of both lactate and ammonia can be used as a screening method for myoadenylate deaminase deficiency (MADD) and for various glyco(geno)lytic defects. A standardized and a nonstandardized test have been compared in a group of 186 patients with exertional myalgia. Standardization of the ischemic forearm test has led to greater yields of both lactate and ammonia in venous return blood of patients and controls. The sensitivity of the proposed test procedure in detecting MADD patients was 100%, whereas the specificity amounted to 98.8% among exertional myalgia patients.

The clinical significance of myoadenylate deaminase (MAD) deficiency and its mode of inheritance is still questioned. There were 36 relatives of 9 unrelated MAD deficient patients who were examined with the aid of a standardized ischemic forearm test: 8 new cases of MAD deficiency were detected, 5 of which were confirmed histochemically and biochemically. Obligate heterozygotes showed a normal ammonia production and MAD staining, but the mean activity of the enzyme was significantly less than in a group of controls. The results obtained from the family study strongly suggest an autosomal recessive mode of inheritance. However, only 2 of the 8 newly found MAD deficient individuals complained of exertional myalgia, whereas the remaining 6 were without any symptoms or complaints. This finding casts doubt on the clinical significance of MAD deficiency and the relationship of the deficiency state with exertional myalgia.