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INTRODUCTION: McArdle disease presents clinical and genetic heterogeneity. There is no obvious association between genotype and phenotype. PYGM (muscle glycogen phosphorylase gene) mRNA expression and its association with clinical, morphological, and genetic aspects of the disease as a set have not been studied previously. METHODS: We investigated genetic variation in PYGM considering the number of PTCs (premature termination codon) per sample and compared mRNA expression in skeletal muscle samples from 15 patients with McArdle disease and 16 controls to PTCs number and different aspects of the disease. RESULTS: The main variant found was c.148C>T (PTC-premature termination codon). Patients with two PTCs showed 42% mRNA expression compared to the control group. Most cases showed an inversely proportional relation among PTCs and mRNA expression. Association between mRNA expression and other aspects of the disease showed no statistically significant difference (p> 0.05). DISCUSSION: mRNA expression is not useful as a predictor factor for the prognosis and severity of the disease. Different mechanisms as post-transcriptional events, epigenetics factors or protein function may be involved.

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McArdle disease (MD) is a metabolic myopathy caused by deficiency of the myophosphorylase enzyme. The aim of our study was to analyse a series of MD patients in Brazil and the correlation between clinical findings, laboratory data, electromyography, muscle biopsy and genetic features. The PYGM gene was analysed by PCR/RLFP and Sanger sequencing. The sample included 12 patients, aged 18-57 years, from unrelated families. Exercise intolerance was present in all cases. Serum creatine kinase levels at rest were increased in all patients. Forearm ischaemic exercise testing in five patients revealed no increase in venous lactate. Needle electromyography presented 'myopathic pattern' in six patients. Muscle biopsy showed vacuolar myopathy in 10 patients and deficiency of myophosphorylase enzyme in all patients. The genetic analysis showed p.R50X as the most common mutation (allelic frequency: 56.25%), other known mutations (p.Y574X, p.G205S, p.W798R, IVS14 + 1G > A and IVS19-1G > A) and a new mutation (p.Asn168Lysfs*15) were also identified. Several features of the disorder were similar to the vast majority of patients worldwide. The genetic findings of this study revealed a range of mutations that are quite similar to the European cohort. The discovery of one novel mutation increases the genotypic heterogeneity of PYGM gene.

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McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.

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McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to ‘growing pains’ and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.

A doença de McArdle é o tipo mais frequente das glicogenoses. A apresentação clínica característica na infância inclui mialgia e intolerância aos esforços/exercício físico. Frequentemente, os sinais e sintomas das crianças não são considerados devidamente, sendo muitas vezes interpretados como “dores do crescimento”, retardando o diagnóstico. Erros diagnósticos não são raros uma vez que outras doenças, como distrofia muscular ou canalopatias musculares, podem apresentar sintomas semelhantes. Entretanto, um simples teste de exercício físico realizado no ambulatório/consultório médico pode ajudar a identificar estes pacientes pois evidencia o fenômeno second wind, patognomônico da doença de McArdle. Aqui é descrito um relato de caso de um paciente ilustrando o valor do simples 12 minutes walk test.

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The rosuvastatin inducing rhabdomyolysis in McArdle disease (MD) has not been reported to date. A 35-years-old man had exercise intolerance, muscular fatigue and cramps during physical activity since infancy. He presented severe rhabdomyolysis episode with seizure and coma after use of rosuvastatin. The investigation showed increased serum creatine-kinase levels and the forearm ischemic exercise did not increase venous lactate. The muscle biopsy showed subsarcolemmal and central accumulation of glycogen and absence of the myophosphorylase enzyme. The statin induced myopathy is discussed and the danger of its use in MD is emphasized.

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The rosuvastatin inducing rhabdomyolysis in McArdle disease (MD) has not been reported to date. A 35-years-old man had exercise intolerance, muscular fatigue and cramps during physical activity since infancy. He presented severe rhabdomyolysis episode with seizure and coma after use of rosuvastatin. The investigation showed increased serum creatinekinase levels and the forearm ischemic exercise did not increased venous lactate. The muscle biopsy showed subsarcolemmal and central acummulation of glycogen and absence of the myophosphorylase enzyme. The statin induced myopathy is discussed and the danger of its use in MD is emphasized.

Rosuvastatina induzindo rabdomiólise na doença de McArdle (MD) não foi relatada até o momento. Descrevemos o caso de um homem de 35 anos que desde a infância apresentava sintomas de intolerância aos exercícios, fadiga muscular e cãibras durante o esforço físico, porém após o uso de rosuvastatina apresentou episódio de rabdomiólise com crises convulsivas e coma. A investigação mostrou creatinoquinase sérica elevada e teste do esforço isquêmico sem aumento no lactato venoso. A biópsia muscular revelou acúmulo central e subsarcolemal de glicogênio nas fibras e ausência da enzima miofosforilase. Discutimos as estatinas induzindo miopatia, enfatizando o risco do seu uso na MD.

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McArdle disease (glycogenosis type V) is a metabolic myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme myophosphorylase. In these patients, the motor nerve conduction studies after a short period of maximal voluntary muscle contraction or repetitive stimulation reveals characteristic findings of the disease. A 37-year-old man presented symptoms of exercise intolerance, muscular fatigue and cramps in the beginning of the physical activity with "second wind" phenomenon. The motor nerve conduction studies after a voluntary contraction of 30 and 90 seconds presented decrease in the amplitude of the compound muscle action potential in median, ulnar and deep peroneal nerves; and decrement after 200 stimulation at the 40 Hz in deep peroneal nerve. The electromyography presented myopathic pattern and during the ischemic exercise electric silence was not proven. The characteristic of electrophysiological studies are discussed with emphasis at the importance of the motor nerve conduction studies in the patients with suspicion of metabolic myopathy.

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McArdle disease (glycogenosis type V) is a metabolic myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme myophosphorylase. In these patients, the motor nerve conduction studies after a short period of maximal voluntary muscle contraction or repetitive stimulation reveals characteristic findings of the disease. A 37-year-old man presented symptoms of exercise intolerance, muscular fatigue and cramps in the beginning of the physical activity with [quot ]second wind[quot ] phenomenon. The motor nerve conduction studies after a voluntary contraction of 30 and 90 seconds presented decrease in the amplitude of the compound muscle action potential in median, ulnar and deep peroneal nerves; and decrement after 200 stimulation at the 40 Hz in deep peroneal nerve. The electromyography presented myopathic pattern and during the ischemic exercise electric silence was not proven. The characteristic of electrophysiological studies are discussed with emphasis at the importance of the motor nerve conduction studies in the patients with suspicion of metabolic myopathy.

A doença de McArdle (glicogenose tipo V) é miopatia metabólica com sintomas de intolerância ao exercício, causados pela deficiência da enzima miofosforilase. Nesses pacientes, o estudo da condução nervosa motora após período de esforço muscular máximo ou ao estímulo repetitivo pode revelar achados característicos da doença. Descrevemos o caso de um homem de 37 anos com sintomas de intolerância aos exercícios, fadiga muscular e cãibras no início da atividade física com a presença do fenômeno de "second wind". O estudo da condução nervosa motora apresentava redução na amplitude do potencial de ação muscular composto após esforço de 30 e 90 segundos em nervos mediano, ulnar e fibular profundo e decremento após 200 estímulos a 40 Hz em nervo fibular profundo. A eletromiografia de agulha apresentava padrão miopático e durante o exercício isquêmico não se evidenciou silêncio elétrico. Discutimos as características eletrofisiológicas enfatizando a importância do estudo da condução nervosa motora e teste de estimulação repetitiva nos pacientes com suspeita de miopatia metabólica.

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This disease was described by McArdle as an inherited autosomal recessive affection characterized by glycogen storage with normal chain in the skeletal muscles, due to absence of myophosphorylase activity. Under a clinical aspect, excessive fatigability, cramps and myoglobinuria appear following physical exercise. A case of this disease in a 36-year-old male patient is reported. Failure of elevation of venous blood lactate after physical effort under anaerobic conditions, as well as muscle histochemistry, made diagnosis confirmation possible. The authors comment on the differential diagnosis between McArdle's disease and the other causes of myoglobinuria, specially phosphofructokinase and carnitine-palmityl-transferase deficiency.

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