Whole-exome sequencing detects PYGM variants in two adults with McArdle disease

McArdle disease is a debilitating glycogen storage disease with typical onset in childhood. Here, we describe a former competitive athlete with early adult-onset McArdle disease and a septuagenarian with a history of exercise intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified biallelic variants in the PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue, and molecular findings for the individuals and add to the knowledge of the genotypic spectrum of this disorder.

Automated summary

McArdle disease is a glycogen storage disease typically onset in childhood. In this case report, a former competitive athlete and a septuagenarian with exercise intolerance since adolescence were both found to have biallelic variants in the PYGM gene. The former athlete had a common pathogenic variant in trans with a novel missense variant, while the second individual had a previously described homozygous missense variant.