Effect of fuels on exercise capacity in muscle phosphoglycerate mutase deficiency.
BACKGROUND
Muscle phosphoglycerate mutase deficiency (PGAMD) is a rare, recessively inherited metabolic myopathy that affects one of the last steps of glycolysis. Clinically, PGAMD resembles muscle phosphorylase deficiency (McArdle disease) and phosphofructokinase deficiency (PFKD). However, it is unknown whether PGAMD is associated with a second-wind phenomenon during exercise, as in McArdle disease, and whether patients with PGAMD, like patients with PFKD and McArdle disease, benefit from supplementation with fuels that bypass the metabolic block.


OBJECTIVE
To investigate whether fuels that bypass the metabolic block can improve exercise capacity or whether exercise capacity improves during sustained exercise.


METHODS
Single-blind, placebo-controlled investigation of the effects of glucose, lactate, and intralipid on work capacity in patients with PGAMD.


METHODS
National University Hospital, University of Copenhagen, and Neuromuscular Center, Institute for Exercise and Environmental Medicine. Patients Two unrelated men (21 and 26 years old) with PGAMD who since their teens had experienced muscle cramps, muscle pain, and episodes of myoglobinuria provoked by brief vigorous exercise, 4 patients with McArdle disease (mean +/- SD age, 32 +/- 5 years) with 0% residual phosphorylase activity in muscle, and 6 healthy, untrained male volunteers (mean +/- SD age, 23 +/- 1 years) were studied.


METHODS
Using constant and variable workload protocols on a cycle ergometer, it was investigated whether a spontaneous second wind occurs during exercise in patients with PGAMD, and using a constant workload protocol followed by an incremental load to exhaustion, it was tested whether infusion of lactate, glucose, or intralipid alters the exercise tolerance in PGAMD.


METHODS
Whether a second wind occurs during exercise and whether fuels that bypass the metabolic block can improve exercise and oxidative capacity.


RESULTS
In contrast to patients with McArdle disease, with whom they share many clinical features, in patients with PGAMD, cycle exercise and oxidative capacity are virtually normal, a second wind does not occur, and lipid and lactate supplements do not improve exercise capacity.


CONCLUSIONS
Although the clinical manifestations of PGAMD mimic McArdle disease with respect to the presence of exertional muscle cramps, rhabdomyolysis, and myoglobinuria, this study shows that cycle exercise responses are strikingly different.
Vissing
John
J
Copenhagen Muscle Research Center, National University Hospital, Denmark. vissing@rh.dk
Quistorff
Bjørn
B
Haller
Ronald G
RG
D000328:Adult; D015444:Exercise; D005080:Exercise Test / Q000379:methods; D005947:Glucose / Q000008:administration & dosage*; D024982:Glycogen Phosphorylase, Muscle Form / Q000172:deficiency; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D043322:Lactase / Q000008:administration & dosage*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010736:Phosphoglycerate Mutase / Q000172:deficiency*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D024982:Glycogen Phosphorylase, Muscle Form; D043322:Lactase; D010736:Phosphoglycerate Mutase; D005947:Glucose