Autosomal recessive inherited inborn error of metabolism,
probably underdiagnosed, characterized by muscle fatigue, myalgia, and
cramping following exercise.
McArdle Disease (or Syndrome, or Myopathy); Muscle
Glycogen Phosphorylase Deficiency; Myophosphorylase Deficiency; Glycogenosis
This inborn error of metabolism was first described in 1951 by
Brian McArdle (1911-2002), a British pediatrician, in a 30-year-old man who complained of pain followed by weakness and
stiffness after exercise.
GSD V accounts for approximately 2.5% of all patients affected with GSD
Autosomal recessive. Although males and
females should be equally affected, more males than females have been
reported. The gene encoding the muscular isoform of phosphorylase is located
on band 11q13. Nonsense, deletion, missense, and splice-junction mutations
usually result in almost complete absence of myophosphorylase in skeletal
muscle. Three common mutations in the gene (R49X, G204S, K542T) account for
approximately 90% of the mutant alleles in the white population.
Deficiency of muscle phosphorylase
(myophosphorylase or alpha-1,4-glucan orthophosphate glycosyl transferase),
which initiates glycogenolysis by removing 1,4-glucosyl groups with release
of glucose-1-phosphate. Myophosphorylase is the only isoform present in
skeletal muscle (but also in the heart and the brain). Patients are unable
to release glucose from glycogen in muscle. The production of adenosine
triphosphate via the Krebs cycle is compromised and the exercising muscle
derives its energy from blood glucose and free fatty acids, which might
account for the second-wind phenomenon experienced by these patients, (i.e., progressive fatigue
and muscle weakness develops after 10 to 15 min of exercise. Following a rapid recovery,
exercise can be resumed without difficulties for a prolonged time period.)
Painful muscle cramps following exercise. No rise in
serum lactate following ischemic exercise. Phosphorus-31 nuclear magnetic
resonance (31P-NMR) shows a lack of cytoplasmic acidification following
exercise. DNA diagnosis possible. No electrical activity may be observed on
EMG during cramps. The disease may be asymptomatic during childhood.
Clinical heterogeneity. Onset often in
adolescence or early adulthood. Weakness and cramping of skeletal muscles
after exercise. May have episodes of rhabdomyolysis and myoglobinuria after
vigorous exercise (half of patients develop acute renal failure). Muscle
wasting develops later. Heart muscle unaffected. Prognosis generally good
with avoidance of excessive exercise. Seizures have been described in 4%
of patients. A rare fatal infantile form is described (hypotonia, diminished
tendon reflexes); death results from respiratory failure as a consequence of
severe muscular weakness. A late-onset form, also very rare, has been reported.
Assess history for episodes of
myoglobinuria and severity of episodes of muscle weakness. Check renal
function, which may be impaired by myoglobinuria. Patients with GSD V may be
depleted in pyridoxine, which is normally bound to myophosphorylase.
Tourniquets may lead to prolonged muscle
cramping, even compartment syndrome, and should be avoided. Maintain
normothermia to prevent shivering in the postoperative period.
Dextrose-containing solutions should be infused perioperatively.
Succinylcholine should be ...