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

Yıl 2019, Cilt: 6 Sayı: 6, 103 - 108, 30.06.2019

Gülden Diniz Canan Çelik Oğuz Dikbaş Aslıhan Duman Ayşe Feyda Nursal

https://doi.org/10.17546/msd.565927

Öz

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.

Anahtar Kelimeler

Mc Ardle Disease, Myopathy, Myophosphorylase

Destekleyen Kurum

yok

Proje Numarası

yok

Teşekkür

We gratefully thank to firm “DONE Genetics and Bioinformatic” for their support in genetic analysis of this case

Kaynakça

• 1. De Castro M, Johnston J, Biesecker L. Determining the prevalence of Mc Ardle disease from gene frequency by analysis of next-generation sequencing data. Genet Med 2015;17(12):1002-6. doi: 10.1038/gim.2015.9
• 2. Vissing J, Duno M, Schwartz M, Haller RG. Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in Mc Ardle disease. Brain 2009; 132 (6): 1545–1552.
• 3. Nadaj-Pakleza AA, Vincitorio CM, Laforet P, Eymard B, Dion E, Teijeira S, et al. Permanent muscle weakness in McArdle disease. Muscle & nerve 2009; 40(3):350-7.
• 4. Satoh A, Hirashio S, Arima T, Yamada Y, Irifuku T, Ishibashi H, et al. Novel Asp511Thr mutation in McArdle disease with acute kidney injury caused by rhabdomyolysis. CEN Case Rep 2019 Mar 21. doi: 10.1007/s13730-019-00392-6
• 5. Scalco RS, Morrow JM, Booth S, Chatfield S, Godfrey R, Quinlivan R. Misdiagnosis is an important factor for diagnostic delay in McArdle disease. Neuromuscul Disord 2017;27(9):852-855. doi: 10.1016/j.nmd.2017.04.013.
• 6. Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martin MA, et al. McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene. Human mutation 2015; 36(7):669-78.
• 7. Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). The Cochrane database of systematic reviews 2014;11:CD003458.