McArdle's disease in a Turkish woman due to an intronic variant of PYGM gene

Abstract

Objective: Glycogen storage disease type 5, also known as McArdle disease, is a hereditary disorder with progressive myopathy. It is characterized by onset of exercise intolerance with premature fatigue and painful muscle cramps in childhood or adolescence. Temporary myoglobinuria may occur after exercise due to rhabdomyolysis. Patients may have mild muscle weakness since childhood. Muscular atrophy with fatty replacement may develop in adult life. McArdle disease is a relatively benign disease and rarely severe myoglobinuria can cause acute renal failure as a complication of widespread rhabdomyolysis. This autosomal recessive disease is caused a homozygous mutation of the PYGM gene encoding muscle enzyme myophosphorylase C. 

Case: A 36-year-old woman admitted to the Physical Medicine and Rehabilitation polyclinic of Giresun University Hospital with a complaint of gradually increasing progressive weakness and tiredness since 13 years age. CK serum level has been found to in normal range; even after exercise. The findings demonstrated myogenic abnormalities on electromyography, multiple glycogen-containing vacuoles and undetectable muscle myophosphorylase activity on muscle biopsy. The genetic analysis revealed no pathogenic mutations in exon regions of PYGM gene. But in sequencing analysis, the rs71049658, insertion/ deletion variation in intron 17 was determined. Coenzyme Q10 (CoQ-10) 30mg/day, vitamin B6 250mg/day and L-carnitine 1gr/day treatment protocol has been applied and after two months the treatment, clinical improvement has been achieved. 

Conclusion: In this case report, an atypical McArdle case with a diagnostic challenge has been presented. We thought that this polymorphism in the myophosphorylase gene may lead to a severe mosaic alteration in mRNA splicing, including exon skipping, activation of cryptic splice-sites, and exon-intron reorganizations.