Late presentation of McArdle Disease: a special focus on symptomatology

Background: Glycogen storage disease type V (or McArdle disease) is a metabolic myopathy whose age of onset is frequently in the first decade of life. However, there are delays in diagnosis due to an overlook in its main symptoms, namely myalgia and fatigability. Thus, late diagnosis are increasingly common.
Case Study / Methods: We present the case of a 75-year-old female patient with a long history of exercise intolerance. For as long as she can remember, when walking she had to stop frequently, with a second wind phenomenon present although not valued. Myalgias worsened in the last 5 years which prompted a more thorough evaluation. Persistent elevation of muscle lesion markers was identified. Iatrogenic, namely due to statins, and inflammatory causes were excluded. A muscle thigh MRI showed lipomatous involution of the hamstrings with bone atrophy and tenuous foci of perifascial edema on both sides. An electromyography showed evidence of myopathy in the proximal and distal muscles of both lower limbs but without evidence of an active inflammatory process. A muscle biopsy was compatible with McArdle disease showing numerous fibers with subsarcolemmal vacuolation of different sizes and configurations that do not stain in hematoxylin+eosin and were strongly PAS positive; staining for myophosphorylase was negative. Molecular study of PYGM gene showed two heterozygous variants: c.2083G>A p.(Gly695Arg), classified as probably pathogenic, and c.2392T>C p.(Trp798Arg), classified as pathogenic.
Discussion/Conclusion: Muscle symptoms are frequently dismissed/overlooked delaying diagnosis of McArdle disease. In this case, a correct clinical evaluation and a higher awareness prompted an evaluation that lead to a diagnosis in a 75 years-old patient. Therapeutic measures were implemented and a family study is ongoing.