Diagnosis of McArdle’s Disease
Many people with McArdle’s disease have been diagnosed only as adults, as for a number of reasons the condition often seems to escape diagnosis in children. People who have the disease can appear quite healthy, and as such the symptoms can be confused with poor conditioning or laziness.
Following evaluation by a neurologist or other physician, diagnosis for McArdle’s disease can be made in one of two ways:
Ischemic Forearm Test
This test is a valuable diagnostic test for a number of metabolic diseases. Speaking generally, the test measures concentration of lactic acid in the blood before and after local exertion of a muscle group. The following protocol description is taken from the University of Florida School of Medicine website:
The test is performed by contracting the forearm to fatigue with a blood pressure cuff inflated to greater than systolic pressure. Antecubital blood samples for lactate and ammonia are collected before and following exercise at 0, 1, 2, 5, and 10 minutes. Ischemia blocks oxidative phosphorylation and ensures dependence on anaerobic glycogenolysis lactate normally rises at least fourfold within 1 to 2 minutes of exercise ammonia rises fivefold within 2 to 3 minutes.
Lactate concetration will rise several-fold under ischemic conditions in normal subjects (o-o-o). There will be no or minimal rise in patients with myophosphorylase deficiency (McArdle’s disease.)
The ischemic forearm test is only moderately uncomfortable to undergo, involving blood samples, a pressure cuff, and a device to squeeze with the hand for forearm muscle contraction, but takes a few hours in order to get blood samples at a resting metabolic rate.
The following is a description of a muscle biopsy performed in order to diagnose McArdle’s disease in an elderly patient. It involves microscopic muscle fiber examination to identify, among other characteristics, large deposits of glycogen:
Biopsy of Left quadriceps was performed. The biopsy showed subsarcolemmal vacuoles in many fibers with no abnormal contents on hematoxylin and eosin (fig. 1A), Masson’s trichrome (fig. 1B) or Gomori stains (Fig.1C). Increased glycogen content (Fig. 2A) was present in several fibers on PAS stain (diastase sensitive). Myophosphorylase activity was absent using enzyme histochemistry (fig. 2B) with a positive control (Fig. 2C). Mild to moderate myopathic features were present including increased fiber size variation and internal nucleation (Fig. 3A) with scattered myofiber hypertrophy and occasional fiber splitting (fig. 3B). Type I fiber smallness was suggested on ATPse stains (fig. 3C). Decreased oxidative enzymes staining with “moth-eaten” appearance was present, mostly in type 1 fibers (fig. 4A) with linearization of the intermyofibrillar architecture in type II fibers (Fig. 4B). Neurogenic atrophy was minimal.
The biopsy looks for the presence of myophosphorylase activity, which is absent in and can confirm diagnosis of McArdle’s disease.
Diagnosis of McArdle’s disease should be made by a physician familiar with metabolic disease of the muscle. To find a Muscular Dystrophy Association clinic near you, click here.