Doença de McArdle: um relato de caso / McArdle's Disease: a case report

RESUMO A Doença de McArdle (DM) ou glicogenose do tipo V, é uma afecção rara que manifesta-se com intolerância ao exercício, crises de mioglobinúria por rabdomiólise e mialgia. Além disso, pode haver deterioração do quadro com insuficiência renal e isquemia muscular associada ao uso de anestésicos inalados e relaxantes musculares. Relata-se um caso clínico de uma mulher de 39 anos que apresentava mialgias em sua adolescência, porém sem diagnósitico, associado a comorbidades que prejudicaram o diagnóstico precoce da Doença de MacArdle. Diagnosticada após internação por pneumonia aspirativa, onde foram evidenciados altos níveis de creatinofosfoquinase e através da biópsia muscular com imuno-histoquímica. PALAVRA-CHAVE: McArdle, miopatia, mialgia, glicogenose tipo V

ABSTRACT McArdle Disease (MD) or glycogenosis type V is a rare condition that manifests with exercise intolerance, myoglobinuria crises caused by rhabdomyolysis, and myalgia. In addition, there may be a deterioration of the condition with renal failure and muscle ischemia associated with the use of inhaled anesthetics and muscle relaxants. We report a clinical case of a 39-year-old woman who had myalgia in her adolescence, but without a diagnosis, associated with comorbidities that hampered the early diagnosis of McArdle Disease. Diagnosed after hospitalization for aspiration pneumonia, where high levels of creatine phosphokinase were evidenced and through muscle biopsy with immunohistochemistry. KEYWORDS: McArdle disease, myopathy, myalgia, glycogenosis type V

McArdle's disease: Diagnostic approach after clinical symptoms of vigorous exercise intolerance in a snowboarder in Alpes / Enfermedad de McArdle: enfoque diagnóstico después de los síntomas clínicos de intolerancia al ejercicio vigoroso en un snowboarder en los Alpes

ABSTRACT McArdle's disease (glycogen storage disease type V) is an energy-dependent disorder of skeletal muscle caused by a deficiency of myophosphorylase, an important enzyme of carbohydrate metabolism that converts glycogen to glucose-1-phosphate. A 46 year-old man was sent to the rheumatology outpatient department with a 3-year history of severe exercise-induced cramps and myalgias. The episodes began when he worked in France and used to practice ski and snowboard in the Alps Mountain, with exercise intolerance, muscle cramps, and myoglobinuria. The laboratory results showed elevated serum creatine kinase levels (~15,000 U/L), and the biopsy of the deltoid muscle revealed glycogen subsarcolemmal vacuoles and absence of myophosphorylase enzymatic activity. This clinical case emphasises the importance of taking into account this metabolic disorder when faced with a patient with exercise intolerance and cramps, especially after vigorous/anaerobic exercise and elevated levels of CK activity. It is fundamental to explain the aetiology of the patient symptoms in order to improve quality of life and avoid unnecessary complications.

R E S U M E N La enfermedad de McArdle (enfermedad de almacenamiento de glucógeno tipo V) es un trastorno del músculo esquelético dependiente de la energía causado por una deficiencia de miofosforilasa, una importante enzima del metabolismo de los hidratos de carbono que convierte el glucógeno en glucosa-1-fosfato. Un hombre de 46 años de edad fue enviado al departamento de reumatología para pacientes ambulatorios con un historial de 3 años de calambres y mialgias severos inducidos por el ejercicio. Los episodios comenzaron cuando trabajó en Francia y solía practicar esquí y snowboard en el macizo de los Alpes, con intolerancia al ejercicio, calambres musculares y mioglobinuria. Las pruebas de laboratorio mostraron niveles elevados de creatina quinasa sérica (~ 15.000 U/l) y la biopsia del músculo deltoides reveló vacuolas subsarcolémicas de glucógeno y ausencia de actividad enzimática de la miofosforilasa. Nuestro caso clínico enfatiza la importancia de pensar en este trastorno metabólico cuando tenemos un paciente con intolerancia al ejercicio y calambres, especialmente después de un ejercicio vigoroso/anaeróbico y niveles elevados de actividad CK. Es fundamental explicar la etiología de los síntomas del paciente para mejorar la calidad de vida y evitar complicaciones innecesarias.

McArdle's disease: an underestimated or underdiagnosed myopathy in rheumatologic practice? Cases series and literature review / Doença de mcardle: uma miopatias subestimada e subdiagnosticada na pratica reumatológica? série clínica e revisão de literatura

OBJECTIVE: McArdle's disease is a metabolic myopathy that manifests with varied clinical conditions and is often confounded with other diagnoses. Herein, the authors report a case series and carry out a literature review. METHODS: A cross-sectional single-center study evaluating 12 patients with McArdle's disease was conducted. RESULTS: Mean age at onset of symptoms was 28.0±17.4 years, while age at disease diagnosis was 39.0±14.8 years. History of intolerance to physical exercises was observed in 10 cases; muscle weakness in 9, second wind phenomenon in only 1 case. The presence of cramps, fatigue and myalgia was observed in 12, 11 and 9 of the cases respectively. Median creatine phosphokinase level was 5951U/L. Most of the patients (83.3%) were initially diagnosed with another condition (polymyositis, inclusion body myositis, fibromyalgia and/or muscular dystrophy), and approximately half had received glucocorticoids and/or immunosuppressants prior to definitive diagnosis. All patients underwent muscular biopsy, which revealed the presence of subsarcolemmal vacuoles characterized by glycogen deposits, and negative histochemical reaction for the myophosphorylase enzyme. CONCLUSION: The present study reinforces the presence of clinical variability among patients and shows that McArdle's disease should be considered one of the differential diagnoses of inflammatory myopathies and other rheumatic diseases.

OBJETIVO: A doença de McArdle é uma miopatia metabólica que se manifesta com condições clínicas variadas e muitas vezes é confundida com outros diagnósticos. Os autores relatam uma série de casos e realizam uma revisão de literatura. MÉTODOS: Estudo transversal de um único centro em que foram avaliados 12 pacientes com doença de McArdle. RESULTADOS: A média de idade no início dos sintomas foi de 28,0±17,4 anos, enquanto a idade no diagnóstico da doença foi de 39,0±14,8 anos. História de intolerância ao exercício físico foi observada em 10 dos casos; fraqueza muscular em 9; fenômeno do "second wind" em apenas 1 caso. A presença de câimbras, fadiga e mialgia foi observada, respectivamente, em 12, 11 e 9 dos casos. O nível mediano de creatinafosfoquinase foi de 5951U/L. Oito pacientes foram inicialmente diagnosticados com outra condição (polimiosite, miosite de corpos de inclusão, fibromialgia e/ou distrofia muscular), e aproximadamente metade havia recebido glicocorticoides e/ou imunossupressores antes do diagnóstico definitivo. Todos os pacientes foram submetidos à biópsia muscular, que revelou a presença de vacúolos subsarcolêmicos caracterizados por depósitos de glicogênio e reação histoquímica negativa para a enzima miofosforilase. CONCLUSÕES: O presente estudo reforça a presença de variabilidade clínica entre pacientes e mostra que a doença de McArdle deve ser considerada um dos diagnósticos diferenciais de miopatias inflamatórias e outras doenças reumáticas.

Falso diagnóstico de caminador en puntillas de pies; sospecha de enfermedad de McArdle / False diagnosis of idiopathic toe walker (ITW); suspicion of McArdle disease

El caminar en puntillas de los pies es una condición patológica en la cual las personas caminan en las puntas de los pies sin presentar ninguna condición ortopédica o neurológica. Se ha encontrado que los caminadores en puntillas de pies presentan diferentes características en los músculos gastrocnemios, el tendón de Aquiles y en el pie. La enfermedad de McArdle es una condición médica autosómica recesiva caracterizada por la baja tolerancia a la actividad física, la atrofia de los músculos de la cintura escapular y, en algunos casos, con episodios de mioglobinuria después de realizar ejercicio vigoroso. Este reporte explica el caso de una paciente diagnosticada como caminadora idiopática en puntillas de pies, pero con los signos clínicos de la enfermedad de McArdle. Este reporte busca comentar las características clínicas que diferencian a los caminadores idiopáticos en puntillas de pies y a los pacientes con la enfermedad de McArdle.

Idiopathic Toe Walking is a pathological condition in which the gait takes place on the tip toes. ITW is diagnosed on the absent of any orthopedic or neurological condition. The physiological characteristics of the gastrocnemios muscles, the Achilles tendon, and the foot of Idiopathic toe walkers are different to individuals that are not affected by toe walking. McArdle disease is a medical autosomal-recessive condition, characterised by low exercise tolerance, muscular atrophy at the shoulder girdle, and in some cases myoglobinuria episodes have been reported after vigorous physical activities. In this case study we present a patient diagnosed as Idiopathic toe walker, but with the clinical characteristics of McArdle diseases. The aim of this case study is to present the clinical characteristics that differentiate these two pathological conditions.

Quando a preguiça é sinônimo de doença - um caso de doença de McArdle / When laziness unveils the disease - a case of McArdle disease / Cuando la pereza es sinónimo de enfermedad - un caso de enfermedad de McArdle

A doença de McArdle é uma doença rara, autossômica recessiva, manifestando-se com intolerância ao exercício, mialgias e crises de mioglobinúria por rabdomiólise. Pode complicar-se com insuficiência renal e isquemia muscular associada a anestésicos inalados e relaxantes musculares. Relata-se um caso clínico de um homem de 38 anos que apresentava queixas repetidas de cansaço, palpitações e "sensação de que o músculo bloqueava e encolhia" (sic) durante o exercício, obrigando-o a parar para recuperar. Este quadro estava presente desde a adolescência e cessava com redução do exercício. Foi avaliado, apresentando uma CPK de 554mcg/L, sem outras alterações, pelo que foi referenciado pela médica de família para consulta em Neurologia. Nesta foi solicitada uma biópsia muscular, que revelou doença de McArdle. O médico de família deve ser capaz gerir os casos que se apresentam inespecificamente, valorizando queixas específicas e persistentes no tempo, estando alerta para as situações que possam sugerir uma doença incomum.

McArdle's disease is a rare, autosomal recessive disease, manifesting through exercise intolerance, myalgia and myoglobinuria crises by rhabdomyolysis. Renal failure and muscular ischemia associated with inhaled anesthetics and muscle relaxants may occur. This is a case of a 38-year-old man who presented repeated complaints of fatigue, palpitations and "feeling that the muscle blocked up and shrunk" (sic) during exercise, forcing him to stop. These complaints occurred since adolescence and ceased with exercise reduction. The patient was evaluated and had a CPK of 554mcg/L, without other alterations in the exams, thus being referred to a Neurology appointment by his family doctor. He then was submitted to a muscular biopsy which later revealed McArdle's disease. The family doctor should be able to manage cases that arise nonspecifically, valuing specific and persistent complaints over time and remain alert for situations that suggest an uncommon disease

La enfermedad de McArdle es una enfermedad rara, autosómica recessiva, manifestándose como intolerancia al ejercicio, mialgias y crisis de mioglobinuria por rabdomiolisis. Puede complicarse con insuficiencia renal e isquemia muscular asociada con anestésicos inhalatorios y relajantes musculares. Presentamos un caso de un hombre de 38 años que había repetidas quejas de fatiga, palpitaciones y "sensación de músculo bloqueado y encogido" (sic) durante el ejercicio físico, lo que le obligó a parar para recuperarse. Este marco estaba presente desde la adolescencia y desaparecía con el cese de ejercicio. El paciente fue evaluado y mediante la presentación de una CPK de 554mcg/L, sin otras alteraciones, se hace referencia a la consulta de Neurologia. En esta se ha hecho una biopsia de músculo que reveló la enfermedad de McArdle. El médico de familia debe ser capaz de manejar los casos que se presentan de manera inespecífica, dando importância a las quejas específicas y persistentes en el tiempo y estar alerta para situaciones que podrían sugerir una enfermedad poco frecuente.

Recurrent Episodes of Rhabdomyolysis after Seizures in a Patient with Glycogen Storage Disease Type V

No abstract available.

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease / De intolerância ao exercício à melhora funcional: o fenômeno second wind na identificação da doença de McArdle

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.

The Significance of Clinical and Laboratory Features in the Diagnosis of Glycogen Storage Disease Type V: A Case Report

Glycogen storage disease type V (GSD-V) is the most common disorder of muscle glycogenosis with characteristic clinical and laboratory findings. A 32-yr-old woman complained of exercise intolerance and myoglobulinuria since early adolescence. She reported several episodes of second-wind phenomenon. Physical examination did not show any neurological abnormality, including fixed muscle weakness or atrophy. Serum creatine kinase level was 1,161 IU/L at rest. The result of the non-ischemic forearm exercise test was compatible with GSD-V. Mutation analysis identified the compound heterozygous mutations of the PYGM, p.D510fs and p.F710del, which has not yet been reported in Korea. The present case recognizes that detail clinical and laboratory analysis is the first step in the diagnosis of GSD-V.

Recurrent acute kidney failure due to mcardle disease

We present an adolescent with McArdle disease and recurrent acute kidney failure due to rhabdomyolysis. The patient was admitted with acute kidney failure for 3 times and due to a history of proximal weakness, fatigue, and muscular cramps after physical activities a glycogen-storage disease was suspected. Serum creatine phosphokinase and urine myoglobin were found to be elevated. McArdle disease was diagnosed based on pathologic examination of muscle tissue specimen. Patients presenting with rhabdomyolysis following strenuous exercise should be evaluated for McArdle disease

McArdle disease with rhabdomyolysis induced by rosuvastatin: case report

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.

Estudo da condução nervosa motora na doença de McArdle: relato de caso / Motor nerve conduction study in McArdle disease: case report

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.

A Case of McArdle's Disease

McArdle's disease is a disorder of carbohydrate metabolism, which is inhented as an autosomal recessive or occasionally an autosomal dominant trait. Hallmark of clinical features is exercise intolerence, I.e. muscle pain following strenuous exercise. Electrophysiologically insertion of an EMG needle shows that there is no electrical activity, differentiating this contracture from a muscle cramp. Histological examination of muscle biopsy specimen shows increase in glycogen and the presence of subsarcolemrnal blebs. We report a 23-year-old, male patient who presented clinical, electrophysiological, and histological findings compatible with McArdle's disease.