Whole-exome sequencing detects PYGM variants in two adults with McArdle disease
- Amanda Thomas-Wilson1,3,
- Avinash V. Dharmadhikari1,3,
- Jonas J. Heymann1,
- Vaidehi Jobanputra1,
- Salvatore DiMauro2,
- Michio Hirano2,
- Ali B. Naini1,2 and
- Mythily Ganapathi1
- 1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York 10032, USA;
- 2Department of Neurology, Columbia University Irving Medical Center, New York, New York 10032, USA
- Corresponding authors: abn2{at}cumc.columbia.edu; mg3560{at}cumc.columbia.edu
Abstract
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.
- acute rhabdomyolysis
- exercise-induced muscle fatigue
- exercise-induced myoglobinuria
- recurrent myoglobinuria
- Received December 8, 2021.
- Accepted January 6, 2022.
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