An elderly diabetic patient with McArdle disease and recurrent rhabdomyolysis: a potential association with late hypoinsulinemia?

Abstract

Background McArdle disease is a myopathy caused by mutations in PYGM gene that is characterized by reduced or absent activity of myophosphorylase. Reports of patients with concomitant McArdle disease and diabetes are scarce. We report a case of a patient with a late diagnosis of McArdle disease and we postulate that symptoms may be related to hypoinsulinemia. Case presentation This report describes the evolution of an elderly diabetic patient with confirmed diagnosis of McArdle’s disease based on the absence of myophosphorylase activity in the analysis of muscle biopsy, and a homozygous mutation in the PYGM gene. The variant – Chr11: 64.525 (p. Asn168*fs) has not been previously described. The diagnosis of McArdle disease was confirmed after two episodes of rhabdomyolysis, at 77 and 81 years of age, as the symptoms were, until then, discrete. The “second-wind phenomenon” was not spontaneously reported, but it was confirmed when directly questioned. We postulate that the later episodes of rhabdomyolysis occurred because of a progressive decrease in insulin production with a consequent reduction in the uptake of blood glucose by muscle cells, thus compromising the cellular energy balance. To our knowledge, this is the first report of recurrent rhabdomyolysis in an elderly diabetic patient with genetically proven McArdle disease. Our initial attempt to reduce insulin resistance with metformin and pioglitazone was not effective, possibly because of inadequate insulinemia. However, an improvement was evident after the administration of low doses of intermediate-acting insulin. Conclusions In view of the patient’s clinical evolution, we suggest the use of medication that reduces insulin resistance for patients with McArdle disease and type 2 diabetes, pre-diabetes or even normoglycemic metabolic syndrome.

Severe Liver Injury Secondary to COVID-19-Induced Rhabdomyolysis in McArdle Disease

“…Several reports have described rhabdomyolysis as a complication of viral infections, including COVID-19 [ 15 ]. The exact mechanisms are still unclear, but they are thought to be related to direct viral-mediated toxic effects on myocytes or elevation of myocyte toxic cytokines [ 16 ].…”

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies

“…GP-MM is encoded by the PYGM gene located on chromosome 11q13 [ 10 ]. A total of 206 pathogenic mutations have been described in this gene [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], with the most prevalent in the Caucasian population (allele frequency ~50%) being the nonsense c.148C>T p.(R50*) variant [ 16 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. There is no association between disease phenotype and PYGM genotype, as the vast majority of mutations generally cause a complete loss of GP-MM activity [ 26 , 31 , 33 , 34 , 35 , 36 ].…”