Myoadenylate deaminase deficiency and forearm ischemic exercise testing

Abstract

Myoadenylate deaminase (MADA) deficiency has been associated with symptoms of postexertional aches, cramps, weakness, and skeletal muscle dysfunction. Measurement of plasma lactate and ammonia concentrations after forearm ischemic exercise has been suggested as a screening test for this disorder. We performed forearm ischemic tests on 3 patients with histochemically defined MADA deficiency and 13 healthy control subjects, in a standardized fashion. Our results demonstrated that subject effort and/or performance during the exercise portion of testing is a critical variable. In addition to lactate and ammonia, plasma purine compounds (adenosine, inosine, and hypoxanthine) were measured. The finding of decreased purine release after exercise in MADA-deficient patients compared with that in normal individuals increases the specificity of the test and supports the hypothesis that disordered purine metabolism occurs in MADA deficiency.Myoadenylate deaminase (MADA) (EC 3.5.4.6) catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine

Forearm Exercise Testing

“…The forearm exercise test in MADD patients produces a normal increase of venous lactate but no rise in ammonia, hypoxanthine, or other ATP degradation products (Fig. 6.3b ) [ 66,67 ] . When enzymatic testing for myoadenylate deaminase and AMPD1 genetic mutation analyses are used as gold standards, the sensitivity of the forearm exercise test for MADD is 100 %, but the speci fi city is 37 % [ 14 ] .…”

“…An increase in serum lactate but not ammonia has been reported in a patient with "exertional myalgia syndrome" who had normal MADD activity in a muscle biopsy specimen [ 68 ] . Measurement of hypoxanthine and other ATP degradation products (IMP and inosine) reportedly increases the speci fi city of forearm exercise test for MADD, but is not usually performed in the clinical setting [ 67,69,70 ] …”

Metabolic myopathies: functional evaluation by different exercise testing approaches

“…The ischemic forearm exercise test allows also a presumptive diagnosis of MADD when a negligible increase in blood ammonia despite a normal rise in lactate occurs [50][51][52].…”

The ischaemic lactate-ammonia test

“…Performance is de®ned as the combination of work and duration and is important, as it became clear that inadequate generation of lactate and ammonia cannot be considered pathological unless adequate effort has been documented during the test. 4 The same authors also concluded, however, that there is no need for elaborate equipment to assess exactly the amount of work performed.…”

“…For example, Valen et al 4 reported that lactate concentrations were increased from a baseline of 1´0 mmol/L (range 1´0±1´8) to 6´4 mmol/L (range 4´0±10´5).…”