McArdle's disease: Molecular genetics and metabolic consequences of the phenotype

McArdle's disease is defined as a lack of functional muscle glycogen phosphorylase. Analysis of the myophosphorylase gene has demonstrated substantial heterogeneity in the mutations that cause the disease, but in almost all individuals, the molecular phenotype is the absence of the protein in skeletal muscle. Muscle glycogen phosphorylase is a major repository of vitamin B 6 in the body, accounting for at least 80% of the total body pool. In McArdle's patients, this pool is therefore missing, introducing the possibility that vitamin B 6 metabolism might be altered in these individuals. Preliminary data have shown that McArdle's patients show signs of a subclinical vitamin B 6 deficiency, and that oral vitamin B 6 supplementation can improve vitamin B 6 status and enhance fatigue resistance in muscle. © 1995 John Wiley & Sons, Inc.