Clinical and laboratory features of patients with myophosphorylase deficiency (McArdle disease)

Miteff, Ferdinand; Potter, Howard; Allen, Jonathan P.; Teoh, H. Heng; Roxburgh, Richard; Hutchinson, David

doi:10.1016/j.jocn.2010.12.033

Cited by 12 publications

(16 citation statements)

References 23 publications

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“…A carefully taken history is essential to diagnose this condition. Exercise intolerance usually starts during the first few minutes of physical activity and is described as muscle pain, discomfort, stiffness, cramps, fatigue and/or exhaustion 2,4,6,7 . It is commonly associated with dyspnoea and tachycardia.…”

Section: Discussionmentioning

confidence: 99%

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

Scalco

Chatfield

Godfrey

et al. 2014

Arq. Neuro-Psiquiatr.

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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.Keywords: McArdle Disease, glycogen storage disease type V, second wind phenomenon, exercise test, 12 minute walk test. RESUMO 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.Palavras-chave: doença de McArdle, doença de depósito do glicogênio tipo V, fenomeno de second wind, teste do exercício, teste 12 minutos de marcha.

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Section: Discussionmentioning

confidence: 99%

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

Scalco

Chatfield

Godfrey

et al. 2014

Arq. Neuro-Psiquiatr.

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“…Mutations in the PYGM gene cause phosphorylase deficiency or its full absence during the course of glycogen metabolism, which impairs the generation of ATP from the breakdown of glycogen [28]. In their study, Zange et al [29] found a reduction of the oxidative phosphorylation rate in 19 individuals with MS. A reduction or absence of glycogen breakdown in the first minutes of exercise training may be one of the main factors associated with the development of fatigue, muscle contracture and cramps, which are usually reported by individuals with MS [30]. Although most MS symptoms usually appear in childhood [30], diagnosis is often established only much later, in adulthood [20].…”

Section: Mcardle Syndromementioning

confidence: 99%

“…In their study, Zange et al [29] found a reduction of the oxidative phosphorylation rate in 19 individuals with MS. A reduction or absence of glycogen breakdown in the first minutes of exercise training may be one of the main factors associated with the development of fatigue, muscle contracture and cramps, which are usually reported by individuals with MS [30]. Although most MS symptoms usually appear in childhood [30], diagnosis is often established only much later, in adulthood [20]. The disease manifestations vary from muscle fatigue, cramps, contracture and intolerance to exercise [24], [20] to more severe conditions, such as myoglobinuria (the presence of myoglobin in the urine, making it darker) and rhabdomyolysis (the breakdown of muscle tissue that leads to the release of muscle fiber contents into blood [31].…”

Section: Mcardle Syndromementioning

confidence: 99%

“…Another striking feature of MS is the fact that, as a function of the reduction of the glycogen oxidation rate with a consequent decrease in the ATP levels, increase of ADP ones [19], which is attended by an exaggerated ammonia response and an increase in the serum creatine kinase level, with the latter being used as a disease marker [30]. The more severe symptoms are related to tubular necrosis that results from rhabdomyolisis [33].…”

Section: Mcardle Syndromementioning

confidence: 99%

“…Exercise has long been considered to be contraindicated in MS patients to avoid problems associated with myoglobinuria [30]. A lack of physical activity may aggravate the problems associated with MS, and the exertion tolerance of the affected individuals may reduce in parallel their oxidative capacity [23].…”

Section: Relationship With Physical Activitymentioning

confidence: 99%

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Neuromuscular, cognitive and metabolic implications of McArdle Syndrome: a global overview

Vieira

Soares

Felipe

et al. 2015

IJBAS

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Carbohydrates are the main source of body energy and they can be stored in the organism in form of glycogen and degraded when there is a need for energy. However, McArdle Syndrome patients exhibit problems to degrade glycogen due to a deficiency in myophosphorylase enzyme, making these patients intolerant to high intensity exercises because a lack of ATP available in muscle cells. It has been found muscular weakness and subsarcolemmal accumulation of glycogen in muscle fibers and in neuronal cells in McArdle Syndrome patients. In its later-onset form, it is associated to muscular dysmorphia, myoglobinuria and rhabdomyolisis. Analyzing the biochemical aspects, it is possible to notice that these patients have a low rate of ATP production due to a reduction in the availability of glucose, reducing oxidative phosphorylation. However, the metabolic "second wind" effect allows the use of other energy sources. Excessively decreased exercise-induced lactate is also characteristic of patients with McArdle Syndrome. Electromyography studies describe alterations in nerve conduction and the necessity of recruiting more motor units to contract muscle in these patients. McArdle Syndrome produces several metabolic changes in patients due to absence of myophophorylase activity. The practice of aerobic exercise acts positively in these patients probably by increasing mitochondrial metabolism.

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McArdle Disease: Update of Reported Mutations and Polymorphisms in thePYGMGene

et al. 2015

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McArdle disease is an autosomal-recessive disorder caused by inherited deficiency of the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), which catalyzes the first step of glycogen catabolism, releasing glucose-1-phosphate from glycogen deposits. As a result, muscle metabolism is impaired, leading to different degrees of exercise intolerance. Patients range from asymptomatic to severely affected, including in some cases, limitations in activities of daily living. The PYGM gene codifies myophosphoylase and to date 147 pathogenic mutations and 39 polymorphisms have been reported. Exon 1 and 17 are mutational hot-spots in PYGM and 50% of the described mutations are missense. However, c.148C>T (commonly known as p.R50X) is the most frequent mutation in the majority of the studied populations. No genotype-phenotype correlation has been reported and no mutations have been described in the myophosphorylase domains affecting the phosphorylated Ser-15, the 280's loop, the pyridoxal 5'-phosphate, and the nucleoside inhibitor binding sites. A newly generated knock-in mouse model is now available, which renders the main clinical and molecular features of the disease. Well-established methods for diagnosing patients in laboratories around the world will shorten the frequent ∼20-year period stretching from first symptoms appearance to the genetic diagnosis.

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Clinical and laboratory features of patients with myophosphorylase deficiency (McArdle disease)

Cited by 12 publications

References 23 publications

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

Neuromuscular, cognitive and metabolic implications of McArdle Syndrome: a global overview

McArdle Disease: Update of Reported Mutations and Polymorphisms in thePYGMGene

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