FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 329:241-245 July 22, 1993 Number 4 Next

	Full Text Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background and Methods Myophosphorylase deficiency (McArdle's disease) is one of the most common causes of exercise intolerance, muscle cramps, and recurrent myoglobinuria. The myophosphorylase gene has been sequenced and assigned to chromosome 11, but the molecular basis of McArdle's disease is not known. We sequenced complementary DNA in 4 patients and studied genomic DNA by restriction-endonuclease analysis in 40 patients with McArdle's disease.

Results Sequence analysis revealed three distinct point mutations: the substitution of thymine for cytosine at codon 49 in exon 1, changing an encoded arginine to a stop codon; the substitution of adenine for guanine at codon 204 in exon 5, changing glycine to serine; and the substitution of cytosine for adenine at codon 542 in exon 14, changing lysine to threonine. Analysis of restriction-fragment-length polymorphisms of appropriate fragments of genomic DNA after amplification with the polymerase chain reaction showed that 18 patients were homozygous for the stop-codon mutation, 6 had different mutations in the two alleles (compound heterozygotes), and 11 were presumed to be compound heterozygotes for a known mutation and an unknown one; only 5 patients had none of the three mutations. All three mutations were present in various combinations in five members of a family in which transmission appeared to be autosomal dominant.

Conclusions McArdle's disease is genetically heterogeneous, but the most common mutation is the substitution of thymine for cytosine at codon 49. These results suggest that in about 90 percent of patients the diagnosis of McArdle's disease can be made from a patient's leukocytes, thus avoiding the need for muscle biopsy.

Source Information

From the H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia-Presbyterian Medical Center, New York.

Address reprint requests to Dr. DiMauro at 4-420 College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, 630 W. 168th St., New York, NY 10032.

Full Text of this Article

This article has been cited by other articles:

• Garcia-Consuegra, I, Rubio, J C, Nogales-Gadea, G, Bautista, J, Jimenez, S, Cabello, A, Lucia, A, Andreu, A L, Arenas, J, Martin, M A (2009). Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA. J. Med. Genet. 46: 198-202 [Abstract] [Full Text]  
• Gomez-Gallego, F, Santiago, C, Moran, M, Perez, M, Mate-Munoz, J L, del Valle, M F., Rubio, J C, Garcia-Consuegra, I, Foster, C, Andreu, I A L, Martin, M A, Arenas, J, Lucia, A (2008). The I allele of the ACE gene is associated with improved exercise capacity in women with McArdle disease. Br. J. Sports. Med. 42: 134-140 [Abstract] [Full Text]  
• Perez, M., Mate-Munoz, J. L., Foster, C., Rubio, J. C., Andreu, A. L., Martin, M. A., Arenas, J., Lucia, A. (2007). Exercise Capacity in a Child With McArdle Disease. J Child Neurol 22: 880-882 [Abstract]  
• Rubio, J. C., Lucia, A., Fernandez-Cadenas, I., Cabello, A., Blazquez, A., Gamez, J., Andreu, A. L., Martin, M. A., Arenas, J. (2006). Novel Mutation in the PYGM Gene Resulting in McArdle Disease. Arch Neurol 63: 1782-1784 [Abstract] [Full Text]  
• Perez, M, Martin, M A, Rubio, J C, Mate-Munoz, J L, Gomez-Gallego, F, Foster, C, Andreu, A L, Arenas, J, Lucia, A, Fleck, S J (2006). Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising * Commentary. Br. J. Sports. Med. 40: 725-726 [Abstract] [Full Text]  
• Ramirez, M, Lucia, A, Gomez-Gallego, F, Esteve-Lanao, J, Perez-Martinez, A, Foster, C, Andreu, A L, Martin, M A, Madero, L, Arenas, J, Garcia-Castro, J (2006). Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury. Br. J. Sports. Med. 40: 719-722 [Abstract] [Full Text]  
• Quintans, B., Sanchez-Andrade, A., Teijeira, S., Fernandez-Hojas, R., Rivas, E., Lopez, M. J., Navarro, C. (2004). A New Rare Mutation (691delCC/insAAA) in Exon 17 of the PYGM Gene Causing McArdle Disease. Arch Neurol 61: 1108-1110 [Abstract] [Full Text]  
• Bruno, C., Bertini, E., Santorelli, F. M., DiMauro, S. (2000). HyperCKemia as the Only Sign of McArdle's Disease in a Child. J Child Neurol 15: 137-138 [Abstract]  
• Fernandez, R., Navarro, C., Andreu, A. L., Bruno, C., Shanske, S., Gamez, J., Teijeira, S., Hernandez, I., Teijeiro, A., Fernandez, J. M., Musumeci, O., DiMauro, S. (2000). A Novel Missense Mutation (W797R) in the Myophosphorylase Gene in Spanish Patients With McArdle Disease. Arch Neurol 57: 217-219 [Abstract] [Full Text]