These disorders are considered together because they are clinically virtually identical and both express themselves by the development of muscle cramps after exercise (actually true physiologic contractures, as described in Chap. 46). In both diseases, an otherwise normal child, adolescent, or adult begins to complain of weakness and stiffness and sometimes pain on using the limbs. Muscle contraction and relaxation are normal when the patient is in repose, but strenuous exercise, either isometric (carrying heavy weights) or dynamic (climbing stairs or walking uphill), causes the muscles to shorten (contracture), a result of their inability to relax. After vigorous exercise, episodes of myoglobinuria are common, in some cases resulting in renal failure. With mild sustained activity, the patient experiences progressive muscle fatigue and weakness, which diminish following a brief pause. The patient can then resume his activities at the original pace (“second-wind” phenomenon). During the second-wind phase, the patient copes with his symptoms by increasing cardiac output and substituting free fatty acids and blood-borne glucose for muscle glycogen (Braakhekke et al).
The primary abnormality in McArdle disease is a deficiency of myophosphorylase, which prevents the conversion of glycogen to glucose-6-phosphate. Phosphofructokinase deficiency (Tarui disease) interferes with the conversion of glucose-6-phosphate to glucose-1- phosphate; the defect in the latter condition is also present in red blood cells (Layzer et al). The mutations for the conditions are named above and located on different chromosomes and analysis of DNA from the patient’s leukocytes can be used for genetic diagnosis. The muscle (M) subunit of the phosphofructokinase protein in Tarui disease is at fault. This defect predominates in Ashkenazi Jewish men.
Clinical variations of these disorders, particularly in severity and age of onset, are well known. Some patients, with no previous symptoms of cramps or myoglobinuria, develop progressive weakness of limb muscles in the sixth or seventh decade. One of these older patients came to our attention because of chronically elevated levels of CK and mild muscle cramping after climbing stairs. In others, rapidly progressive weakness became evident in infancy, with early death from respiratory failure. Curiously, these extreme forms are not directly related to severity of the enzyme deficiencies.