This test is of value in the diagnosis of McArdle's disease, glycolytic enzyme defects and myoadenylate deaminase deficiency. McArdle's disease (glycogen storage disease type V) is due to muscle phosphorylase deficiency, and typically presents with painful muscle cramps induced by exercise which prevent further exercise. Myoadenylate deaminase deficiency can cause fatigue, cramps and exertional myalgia. However, complete deficiency of this enzyme can be entirely asymptomatic.
Have the appropriate tubes labelled and ready, together with ice for transport to the lab.
After 30 min. at rest , take baseline venous samples from one arm in the usual manner. Then a BP cuff is placed around the upper arm on the other side and inflated to 30 mm above systolic pressure. (One study reports that this cuff is unnecessary (2)). The patient performs maximal strength contractions of the hand at 1 per second for 60 seconds. (e.g. by squeezing on a handgrip exerciser or a second inflated BP cuff). The one second time intervals should be called out for the patient. It is critical that the patient give maximal contractions, particularly in the final 20 seconds when discomfort occurs. If extreme pain occurs, abort the test, as a compartment syndrome has been reported in a patient with myophosphorylase deficiency.
The cuff is then deflated and a 23G butterfly needle quickly inserted into the a vein at the ipsilateral elbow. Tape this into position. Take samples at 1, 3, 5 and 10 min after deflation.
Specimens:
5 sets of samples taken : baseline, +1 min, +3 min, +5 min and +10 min.
2 samples at each time point:
a) 5 mL fluoride tube for lactate
b) 5 mL heparin tube for ammonia.
Place samples immediately on ice. Complete a separate form for each time point ( 5 forms), showing time of collection, and requesting lactate and ammonia on each form. Attach "urgent" stickers to each form, as the ammonia samples need to be rapidly processed. After all samples are collected, send them immediately to the laboratory on ice.
It is advisable to contact the Chemical Pathologist on duty before performing the test, to ensure the samples are handled correctly by the laboratory.
The normal response is a rise in lactate and ammonia, maximal at 1 min. with a gradual decline thereafter.
Lactate should rise by at least 2-fold (usually 5 to 6-fold), with absolute rise of at least 1.9 mmol/L in men or 0.6 mmol/L in women (1)
There is a failure of lactate to rise in McArdles disease and in defects of glycolysis such as deficiency of Phosphofructokinase, Debrancher enzyme, Phosphogycerate Kinase, Phosphoglycerate Mutase, Lactate Dehydrogenase, and sometimes Phosphorylase b Kinase.
Ammonia should increase by at least 1.4-fold (usually 2-3 fold) (1)
Failure of ammonia to rise may be due to inadequate ischaemic exercise, or to myoadenylate deaminase deficiency. There is an exaggerated ammonia rise in McArdles disease.
The lactate/ammonia ratio at +1 min. is a useful parameter: normal >17; McArdles 1-12 (both lactate and ammonia expressed in mmol/L).
The normal baseline lactate is <2.2 mmol/L. A raised baseline lactate may suggest a mitochondrial myopathy.
This protocol was drawn up by James Davidson (LabPlus) and David Hutchinson (Neurology)
Auckland City Hospital, October 2007
1. Tarnopolsky M et al. Diagnostic utility of a modified forearm ischaemic exercise test. Muscle Nerve 2003; 27:359-66
2. Kazemi-Esfarjani P et al. A nonishcaemic forearm exercise test for McArdle disease. Ann Neurol 2002; 52:153-9
3. Livingstone C et al. The ishaemic lactate-ammonia test. Ann Clin Biochem 2001; 38:304-310