Genetic confirmation

• Due to the ultra rare nature of McArdle disease, mistakes have been made in diagnosis [1].

• If patient has an atypical presentation, check whether they have been genetically confirmed.

• DNA analysis of the PYGM gene may be undertaken [2] from blood taken locally.

• Over 150 causative mutations identified to date.

• There is a significant preponderance of the two most common mutations.

[1] McArdle Disease: a clinical review. Quinlivan R, Buckley J, James M, et al. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp. 2009.195040.

[2] Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase. Burke J, Hwang P, Anderson L, Lebo R, Gorin F, and Fletterick R. (1987) Proteins 2: 177-187.

Inheritance

• McArdle disease is inherited in an autosomal recessive pattern [1].

• General practices are very unlikely to see a second patient, other than possibly a sibling.

• Prevalence has been estimated at 1:100,000, based on a carrier frequency of approx. 1:160 [2,3]. In many countries less than half of cases are identified.

• The risk of a patient partnering with a carrier and their child having McArdle’s is approx. 1 in 320.

• For patients of childbearing age, referral for genetic counseling may be appropriate.

[1] Online Mendelian Inheritance in Man. http://omim.org/entry/232600

[2] Treatment of McArdle disease. Haller RG. Arch Neurol 2002; 57:923–4.

[3] A novel mutation in the PYGM gene in a family with pseudo-dominant transmission of McArdle Disease. Isackson PJ, Tarnopolsky M, and Vladutiu GD (2005) Mol Genet Metab, 85: 239-242.