Treatment for McArdle’s Disease
Abstracts & Commentary
Sources: Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle’s disease. N Engl J Med. 2003;349:2503-2509; Amato AA. Sweet success— A treatment for McArdle’s disease. 2004;349:2481-2482.
In this simple yet elegant, single-blind, placebo-controlled, crossover study, 12 patients with McArdle’s disease were given a sucrose, or artificially sweetened placebo load, prior to aerobic exercise to determine if this might improve exercise tolerance. Average age of the 7 men and 5 women was 37 years, and all had lifelong exercise intolerance, episodic muscle cramps, and myoglobinuria triggered by exercise. Diagnosis was confirmed in all by absence of myophosphorylase staining on muscle biopsy and absence of myophosphorylase activity on biochemical muscle testing. Patients were tested after an overnight fast, with 75 g of sucrose or placebo being administered, on alternate days, by a 660 mL caffeine-free soft drink. Exercise began 30-40 minutes later, and periodic blood tests were drawn for glucose, lactose, pyruvate, ammonia, free fatty acids, and insulin measurements. Primary end points included perceived exertion level scored by the patient, each minute of exercise on a 6 (least effort) to 20 (most effort) Borg scale, and heart rate. Statistical analysis was provided by paired Student’s t-test and analysis of variance, with a P value of .05 or less considered significant.
Borg-scale rating of effort significantly improved, and maximal heart rate significantly dropped following sucrose ingestion compared to placebo. Hyperinsulinemia and hyperglycemia followed sucrose load and remained elevated during the exercise period, whereas lactate and pyruvate increased following sucrose ingestion but fell during exercise. Free fatty acids fell, and the (expected) exercise-induced hyperammonemia was attenuated with sucrose. Sucrose ingestion prior to exercise improves exercise tolerance in patients with McArdle’s disease and may prevent exercise-induced rhabdomyolysis.
Originally described in 1951, McArdle’s disease is the first described metabolic myopathy resulting from a single enzyme deficiency, myophosphorylase, needed to convert glycogen to glucose-1-phosphate and lactate. Localized to chromosome 11q13, it is an autosomal recessive disorder usually resulting from a nonsense mutation at codon 49 in exon 1 (R49X), although rare mutations in the coding regions, splice junctions, and exon 2 also occur.1
Diagnosis of a glycogen storage myopathy can usually be made by the forearm exercise test. Following 1 minute of non-ischemic exercise (patient rapidly and vigorously opens and closes his fist), blood ammonia levels rise over the ensuing 10 minutes (indicating adequate exercise has been performed), but lactate levels do not. However, partial deficiency may result in normal lactate production, and specific enzymatic diagnosis requires muscle biopsy with myophosphorylase staining or biochemical assay to demonstrate its deficiency. — Michael Rubin
Dr. Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
1. Deschauer M, et al. Muscle Nerve. 2003;27:105-107.