Case Presentation: An otherwise healthy 17-year-old female presented with arm pain and dark urine after riding a roller coaster. She was found to have a creatine kinase >32,000 with elevated liver enzymes and was admitted for treatment of rhabdomyolysis. She had been admitted a year and a half prior with rhabdomyolysis and compartment syndrome requiring urgent fasciotomy after moving a piece of furniture. She was admitted eight months later for a second episode of rhabdomyolysis after developing arm pain and swelling while sleeping. During her second admission, neurologic, rheumatologic, and genetic workups were initiated due to concern for underlying neuromuscular disease versus inflammatory, metabolic, or inherited myopathy. The patient was discharged from the hospital before work-up was completed. She was scheduled to establish with outpatient genetics/metabolism but was lost to follow-up. Following her third hospitalization, genetic testing was pursued and resulted positive for two variants in the PYGM gene consistent with a diagnosis of McArdle Disease.
Discussion: McArdle Disease, also known as glycogen storage disorder V (GSDV), is an autosomal recessive disorder caused by mutations in the PYGM gene which result in deficiency of myophosphorylase. This prevents glycolysis, resulting in impaired energy production in skeletal muscles during exertion, as well as deposition and build-up of glycogen between myofibrils. Patients with GSDV often have a long history of exercise intolerance leading up to diagnosis. GSDV typically presents with significant fatigue, weakness, muscle cramping, and pain within the first several minutes of activity. Prolonged exercise can result in severe complications such as compartment syndrome, rhabdomyolysis, and acute renal failure. Prevalence of GSDV has long been estimated to be about 1 in 100,000 in the United States. Most patients have symptom-onset prior to age 15; however, the average age of diagnosis is around 37 years, likely due to the often-non-specific nature of symptoms. More recent analysis of gene frequency and next-generation sequencing data estimates the true prevalence to be closer to 1 in 8,000. The discrepancy in estimated prevalence is attributed to late or missed diagnoses. Patients with GSDV have higher rates of obesity, thyroid dysfunction, and coronary artery disease, as well as increased risk for insulin resistance compared with the general population. Given the risk for acute complications necessitating hospitalization and the risk for serious comorbidities later in life, early diagnosis of McArdle Disease is crucial. Early counseling on lifestyle modifications and injury prevention can improve quality of life and long-term functional outcomes while reducing symptom severity, hospitalizations, and medical comorbidities.
Conclusions: The purpose of this case is to describe a severe presentation of a rare glycogen storage disorder that manifested as recurrent, non-traumatic rhabdomyolysis in an otherwise healthy 17-year-old patient. This patient had a delayed diagnosis after being lost to follow up, and her non-specific history without exercise intolerance is atypical for McArdle disease. This case highlights the importance of considering genetic and metabolic etiologies of myopathy in patients hospitalized with rhabdomyolysis, particularly rhabdomyolysis without a clear mechanism.