Asunto(s)
Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V , Parálisis Periódica Hipopotasémica/diagnóstico , Adulto , Consanguinidad , Creatina Quinasa/sangre , Diagnóstico Diferencial , Tolerancia al Ejercicio/fisiología , Pruebas Genéticas , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Humanos , Masculino , Fatiga Muscular/genética , Debilidad Muscular/diagnóstico , Debilidad Muscular/etiología , Mutación Missense , LinajeAsunto(s)
Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Mutación/genética , Adulto , Brasil , Variación Genética/genética , Glucógeno Fosforilasa de Forma Muscular/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Humanos , Masculino , LinajeRESUMEN
Gout disease is an inflammatory arthritis that arises due to the accumulation of monosodium urate crystals (MSU) around the joints and in tissues. Clinical manifestation of metabolic diseases leading to secondary hyperuricemia most predominantly occurs in the form of gouty arthritis. Hyperuricemia and gout may develop during the course of glycogen storage diseases (GSD), particularly in GSD type I, which involves the liver. On the other hand, during the course of GSD type V (GSDV, McArdle's disease), which merely affects the muscle tissue due to the deficiency of the enzyme myophosphorylase, hyperuricemia and/or gout is rarely an expected symptom. These patients may mistakenly be diagnosed as having idiopathic hyperuricemia and associated gout, leading to the underlying secondary causes be overlooked and thus, diagnostic delays may occur. In this case report, we present a premenopausal female patient who experienced flare-ups of chronic arthritis while on disease-modifying antirheumatic drugs and intraarticular steroids due to a diagnosis of undifferentiated arthritis. The patient was initially suspected of having gouty arthritis because elevated concentrations of uric acid were incidentally detected, but then, a diagnosis of asymptomatic GSDV was made owing to elevated concentrations of muscle enzymes during colchicine use. Our aims were to remind rheumatologists of the phenomenon of "myogenic hyperuricemia" and to discuss the potential causes of hyperuricemia that develop during GSD along with the available literature.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Hiperuricemia/complicaciones , Hiperuricemia/diagnóstico , Adulto , Antirreumáticos/uso terapéutico , Artritis/complicaciones , Artritis/tratamiento farmacológico , Artritis Gotosa/sangre , Artritis Gotosa/diagnóstico , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Humanos , Hiperuricemia/sangre , Hiperuricemia/patología , Inflamación , Polimiositis/sangre , Polimiositis/complicaciones , Polimiositis/patología , Ácido Úrico/sangreRESUMEN
PURPOSE OF REVIEW: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. RECENT FINDINGS: The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. SUMMARY: Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo VII/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Miopatías Mitocondriales/diagnóstico , Rabdomiólisis/diagnóstico , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Enfermedad del Almacenamiento de Glucógeno Tipo VII/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo VII/genética , Glucogenólisis/fisiología , Humanos , Masculino , Errores Innatos del Metabolismo/sangre , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Persona de Mediana Edad , Miopatías Mitocondriales/sangre , Miopatías Mitocondriales/genética , Enfermedades Musculares/sangre , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Rabdomiólisis/sangre , Rabdomiólisis/genética , Adulto JovenRESUMEN
PURPOSE: McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs). METHODS: We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients. RESULTS: Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies. CONCLUSION: We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.Genet Med 18 11, 1128-1135.
Asunto(s)
Glucógeno Fosforilasa de Forma Muscular/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Patología Molecular/métodos , Adolescente , Adulto , Codón sin Sentido/genética , Femenino , Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Humanos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Empalme del ARN/genética , Eliminación de Secuencia/genética , Adulto JovenRESUMEN
McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence of myophosphorylase activity in skeletal muscle biopsies and genetic analysis of the myophosphorylase-encoding gene, PYGM. The recently reported association between myophosphorylase and Rac1 GTPase in a T lymphocyte cell line prompted us to study myophosphorylase expression in white blood cells (WBCs) from 20 healthy donors and 30 McArdle patients by flow cytometry using a fluorescent-labeled PYGM antibody. We found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001). PYGM mRNA levels were also lower in white blood cells from McArdle patients. Nevertheless, in 13% of patients (who were either heterozygotes or homozygotes for the most common PYGM pathogenic mutation among Caucasians (p.R50X)), the percentage of myophosphorylase-positive white blood cells was not different compared with the control group. Our findings suggest that analysis of myophosphorylase expression in white blood cells might be a useful, less-invasive, complementary test for diagnosing McArdle disease.
Asunto(s)
Glucógeno Fosforilasa de Forma Muscular/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Leucocitos/enzimología , Adulto , Anciano , Biomarcadores/sangre , Niño , Estudios de Cohortes , Femenino , Citometría de Flujo , Técnicas de Genotipaje , Glucógeno Fosforilasa de Forma Muscular/genética , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/enzimología , Mutación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T/enzimología , Adulto JovenRESUMEN
INTRODUCTION: Creatine kinase (CK) and myoglobin (Mb) do not possess all good qualities as biomarkers of skeletal muscle damage. We investigated the utility of troponin I (TnI) and telethonin (Tcap) as markers and examined their temporal profiles after skeletal muscle damage. METHODS: Plasma profiles were measured before and after exercise in 3 groups: subjects affected by either Becker muscular dystrophy or McArdle disease, and healthy subjects. RESULTS: Mb and TnI appeared early in the blood, and the increase of TnI was only observed in patients with muscle disease. The CK increase was more delayed in plasma. Tcap was not detectable at any time. CONCLUSIONS: Our results suggest that TnI is a marker of more severe damage signifying sarcomeric damage, and it could therefore be an important supplement to CK and Mb in clinical practice. Tcap is not useful as a marker for skeletal muscle damage.
Asunto(s)
Conectina/sangre , Ejercicio Físico/fisiología , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Músculo Esquelético/fisiopatología , Distrofia Muscular de Duchenne/fisiopatología , Troponina I/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Creatina Quinasa/metabolismo , Metabolismo Energético/fisiología , Femenino , Glucógeno/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Humanos , Masculino , Persona de Mediana Edad , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/sangre , Proyectos Piloto , Sarcómeros/metabolismo , Sarcómeros/patología , Adulto JovenRESUMEN
INTRODUCTION: Mc Ardles disease, also known as Type V glycogen storage disease, is a rare deficiency of the enzyme glycogen phosphorylase in muscle cells, inherited as an autosomal recessive trait. In the absence of this enzyme, muscles cannot break down glycogen during exercise, so in patients affected by McArdles disease even moderate physical activity produces cramps, pain and fatigue. Anaerobic activity leads to severe fixed contractures and rhabdomyolisis with myoglobinuria and raised serum creatine-kinase, which, in turn, can lead to acute renal failure. Disease onset is usually in early childhood, although diagnosis is often not made until the second or third decade. CASE REPORT: We present the case of a 68-year-old man who presented to the Emergency Room with fatigue, vertigo, diarrhea and oliguria. The patient underwent five daily hemodialysis sessions, diuresis reappeared and there was progressive recovery of renal function. The patient described episodes of fatigue and muscular pain occurring since childhood: the positive personal history, together with persistently raised CPK levels in the absence of any infective or toxic cause of myositis, led us to suspect the presence of this rare metabolic disease, which was subsequently confirmed by muscle biopsy. CONCLUSION: To date, there is no specific treatment for type V glycogenosis, although a diet rich in protein and saccarose, vitamin B6 supplementation and creatine administration are generally recommended. Moderate physical activity can help manage symptoms by improving exercise tolerance and blood supply to the muscles, ensuring provision of glucose and free fatty acids for the muscle fibers.
Asunto(s)
Lesión Renal Aguda/etiología , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Diálisis Renal , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Anciano , Biomarcadores/sangre , Biopsia , Creatina Quinasa/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/terapia , Humanos , Masculino , Músculos/patología , Diálisis Renal/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD). METHODS: Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects. RESULTS: Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 µmol/L; control peak range 60-113 µmol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion. CONCLUSION: Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P(i) at high exercise intensities.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Enfermedad del Almacenamiento de Glucógeno/enzimología , Músculo Esquelético/enzimología , Fosforilasa Quinasa/deficiencia , Adulto , Anciano , Amoníaco/sangre , Biopsia , Metabolismo de los Hidratos de Carbono/genética , Creatina Quinasa/sangre , Ejercicio Físico , Prueba de Esfuerzo , Antebrazo/irrigación sanguínea , Variación Genética , Glucógeno/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Glucogenólisis , Humanos , Isquemia , Lactatos/sangre , Metabolismo de los Lípidos/genética , Masculino , Músculo Esquelético/metabolismo , Consumo de Oxígeno , Dolor/etiología , Fenotipo , Fosforilasa Quinasa/genética , Flujo Sanguíneo RegionalRESUMEN
INTRODUCTION: McArdle disease is a hereditary myopathy caused by muscle phosphorylase deficiency. Patients experience painful muscle cramps after strenuous exercise; the condition is sometimes associated with rhabdomyolysis, myoglobinuria and resulting acute renal failure. CASE DESCRIPTION: A 12-year-old boy visited the Paediatric and Neurology outpatients' departments with symptoms of leg myalgia, occurring during the warming-up phase of soccer practice, which disappeared after a short rest. Detailed history-taking revealed that he already experienced pain while walking during early childhood. An elevated serum creatine kinase concentration in combination with the typical presentation led to the presumptive diagnosis 'McArdle disease', which was confirmed by molecular genetic analysis. CONCLUSION: There is no effective gene therapy; a multidisciplinary approach by a neurologist, paediatrician, physiotherapist and nutritionist is advised.
Asunto(s)
Ejercicio Físico/fisiología , Glucógeno Fosforilasa de Forma Muscular/deficiencia , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Músculo Esquelético/enzimología , Niño , Creatina Quinasa/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Humanos , Masculino , Dolor/diagnóstico , Dolor/etiologíaRESUMEN
PURPOSE: Increased blood lactate concentration has been suggested as a primary stimulus for the exercise-induced growth hormone response (EIGR). Patients with McArdle disease are unable to produce lactate in response to exercise and thus offer a unique model to assess the role of lactate in the EIGR. Accordingly, McArdle's patients were exercised to test the hypothesis that lactate is a major stimulus of the EIGR. METHODS: 11 patients with McArdle disease (3 male, 8 female; age: 35.5 (SD 13.9) years, height: 166 (8) cm, body mass: 75.2 (13.1) kg) were recruited for the study. The patients walked initially at 0.42 m/s, increasing by 0.14 m/s per 3 min stage. Exercise was terminated when participants completed 3 minutes at 1.80 m/s or when a Borg CR10 pain scale rating of "4" was reached. Stages were separated by 60 s for capillary blood sampling for analysis of hGH and blood lactate concentration. RESULTS: McArdle's patients' blood lactate levels remained at resting levels (0.3-1.2 mmol/l) as exercise intensity increased. Nine out of 11 participants failed to demonstrate an EIGR obtaining hGH values below the clinical definition of a response (>3 microg/l). CONCLUSION: The absence of an EIGR in nine out of 11 participants suggests that lactate could play a major role in the EIGR in humans.
Asunto(s)
Ejercicio Físico/fisiología , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Hormona de Crecimiento Humana/metabolismo , Ácido Láctico/metabolismo , Adolescente , Adulto , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Caminata , Adulto JovenRESUMEN
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.
Asunto(s)
Fluorobencenos/efectos adversos , Enfermedad del Almacenamiento de Glucógeno Tipo V/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Pirimidinas/efectos adversos , Rabdomiólisis/inducido químicamente , Sulfonamidas/efectos adversos , Adulto , Fluorobencenos/uso terapéutico , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Pirimidinas/uso terapéutico , Rabdomiólisis/sangre , Rabdomiólisis/patología , Rosuvastatina Cálcica , Sulfonamidas/uso terapéuticoRESUMEN
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.
Asunto(s)
Adulto , Humanos , Masculino , Fluorobencenos/efectos adversos , Enfermedad del Almacenamiento de Glucógeno Tipo V/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Pirimidinas/efectos adversos , Rabdomiólisis/inducido químicamente , Sulfonamidas/efectos adversos , Fluorobencenos/uso terapéutico , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirimidinas/uso terapéutico , Rabdomiólisis/sangre , Rabdomiólisis/patología , Sulfonamidas/uso terapéuticoRESUMEN
The authors analyzed muscle biopsy specimens of 104 patients with creatine kinase activity greater than 500 UI/L (normal 10 to 170 UI/L) without signs of muscle weakness. They achieved a definite or probable diagnosis in 55% of cases. The most frequently identified diseases were glycogen storage diseases, muscular dystrophies, and inflammatory myopathies. The probability of making a diagnosis was higher in children and when creatine kinase level was greater than 2,000 UI/L.
Asunto(s)
Forma MM de la Creatina-Quinasa/sangre , Enfermedades Neuromusculares/sangre , Adolescente , Adulto , Anciano , Biomarcadores , Biopsia , Niño , Preescolar , Estudios de Cohortes , Distrofina/deficiencia , Fatiga/sangre , Fatiga/etiología , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Calambre Muscular/sangre , Calambre Muscular/etiología , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Enfermedades Neuromusculares/diagnóstico , Estudios RetrospectivosRESUMEN
STUDY OBJECTIVES: Muscle is one of the most commonly affected organs in mitochondrial disorders, and the symptoms are often exercise related. The cardiopulmonary exercise test with the determination of lactic acid formation could give supplementary information about the exercise-induced metabolic stress and compensatory mechanisms used in these disorders. The aim of this study was to evaluate the exercise capacity and lactate kinetics related to exercise in subjects with two genetically characterized mitochondrial disorders (multiple mitochondrial DNA deletions with PEO, MELAS) compared with lactate kinetics in subjects with metabolic myopathy (McArdle's disease) and in the healthy controls. DESIGN: The subjects were consecutive, co-operative patients of Department of Neurology of Helsinki University Hospital. Molecular genetic analyses were used for group classification of the mitochondrial myopathy. STUDY SUBJECTS: The study groups consisted of 11 patients with multiple deletions (PEO) and five patients with a point mutation in the mitochondrial DNA (MELAS), four patients with a muscle phosphorylase enzyme deficiency (McArdle's disease) and 13 healthy controls. The clinical disease of the patients was relatively mild. MEASUREMENTS AND RESULTS: A graded exercise test with ventilatory gas analyses and venous blood lactic acid analyses was performed. The main finding was the prolonged accumulation of blood lactate after the exercise in the PEO and MELAS groups compared with the controls. An overcompensation in ventilation was found in the MELAS and PEO group. CONCLUSIONS: The blood lactate accumulation after exercise occurs in patients with multiple mitochondrial DNA deletions or MELAS even in patients with only mild exercise intolerance. Cardiopulmonary exercise can be used in the diagnostic process of patients with mitochondrial myopathies.
Asunto(s)
ADN Mitocondrial/genética , Ejercicio Físico , Eliminación de Gen , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Ácido Láctico/sangre , Miopatías Mitocondriales/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Humanos , Síndrome MELAS/sangre , Síndrome MELAS/genética , Síndrome MELAS/fisiopatología , Masculino , Persona de Mediana Edad , Miopatías Mitocondriales/sangre , Miopatías Mitocondriales/genética , Oftalmoplejía/sangre , Oftalmoplejía/genética , Oftalmoplejía/fisiopatología , Mutación PuntualRESUMEN
OBJECTIVE: The spontaneous second wind in myophosphorylase deficiency (MD, McArdle's disease) represents a transition from low to a higher exercise capacity attributable to increased oxidation of blood-borne fuels, principally glucose and free fatty acids. Muscle phosphofructokinase deficiency (PFKD) blocks the metabolism of muscle glycogen and blood glucose. The authors inquired whether the additional restriction in glucose metabolism in PFKD prevents a spontaneous second wind. METHODS: The authors compared the ability of 29 patients with MD and 5 patients with muscle PFKD to achieve a spontaneous second wind during continuous cycle exercise after an overnight fast. Patients cycled at a constant workload for 15 to 20 minutes (3 MD patients, 3 PFKD patients) and at variable workloads in which peak exercise capacity was determined at 6 to 8 minutes of exercise and again at 25 to 30 minutes of exercise (29 MD patients, 4 PFKD patients). Heart rate was monitored continuously, and perceived exertion (Borg scale) was recorded during each minute of exercise. Oxygen utilization and blood levels of lactate and ammonia were determined at rest and during peak workloads. RESULTS: All variables in both patient groups were similar at 6 to 8 minutes of exercise. Thereafter exercise responses diverged. Each MD patient developed a second wind with a decrease in heart rate and perceived exertion and an increase in work and oxidative capacity. In contrast, no PFKD patient developed a spontaneous second wind. CONCLUSIONS: Patients with muscle phosphofructokinase deficiency are unable to achieve a spontaneous second wind under conditions that consistently produce one in patients with McArdle's disease. The authors conclude that the ability to metabolize blood glucose is critical to the development of a typical spontaneous second wind.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo VII/fisiopatología , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Fatiga Muscular , Esfuerzo Físico , Adolescente , Adulto , Amoníaco/sangre , Niño , Prueba de Esfuerzo , Ayuno , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo VII/sangre , Frecuencia Cardíaca , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Consumo de Oxígeno , Intercambio Gaseoso Pulmonar , Recuperación de la Función , Factores de TiempoRESUMEN
BACKGROUND: Energy metabolism in muscles relies predominantly on the breakdown of glycogen early in exercise. In patients with McArdle's disease, blocked glycogenolysis in muscles results in low exercise tolerance and can lead to muscle injury, particularly in the first minutes of exercise. We hypothesized that ingesting sucrose before exercise would increase the availability of glucose and would therefore improve exercise tolerance in patients with McArdle's disease. METHODS: In a single-blind, randomized, placebo-controlled crossover study, 12 patients with McArdle's disease drank 660 ml of a beverage that had been sweetened with artificial sweeteners (placebo) or with 75 g of sucrose after an overnight fast. Thirty to 40 minutes later, the patients rode a stationary bicycle at a constant workload for 15 minutes while the heart rate, level of perceived exertion, and venous blood glucose levels were monitored. RESULTS: Supplemental sucrose increased the mean plasma glucose level by more than 36 mg per deciliter (2.0 mmol per liter) and resulted in a marked improvement in exercise tolerance in all patients. The mean (+/-SE) heart rate dropped by a maximum of 34+/-3 beats per minute (P<0.001), and the level of perceived exertion fell dramatically when the patients ingested glucose as compared with when they received the placebo. CONCLUSIONS: This study suggests that the ingestion of sucrose before exercise can markedly improve exercise tolerance in patients with McArdle's disease. The treatment takes effect during the time when muscle injury commonly develops in these patients. In addition to increasing the patients' exercise capacity and sense of well-being, the treatment may protect against exercise-induced rhabdomyolysis.
Asunto(s)
Tolerancia al Ejercicio/efectos de los fármacos , Enfermedad del Almacenamiento de Glucógeno Tipo V/tratamiento farmacológico , Sacarosa/uso terapéutico , Administración Oral , Adulto , Glucemia/metabolismo , Estudios Cruzados , Prueba de Esfuerzo , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Frecuencia Cardíaca , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Método Simple Ciego , Sacarosa/farmacologíaRESUMEN
Two cases of hypercholesterolaemic patients are presented in whom raised plasma creatine kinase was noted during treatment with statins. The plasma creatine kinase failed to fall following cessation of therapy. Further investigation revealed the aetiology of the raised plasma creatine kinase to be due to previously undiagnosed glycogen storage diseases (McArdle's and Pompe's diseases).
Asunto(s)
Creatina Quinasa/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo II/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Simvastatina/farmacología , Adulto , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Humanos , Masculino , Valores de Referencia , Simvastatina/efectos adversosRESUMEN
A 14-month-old girl was hospitalized due to repeated hyper-creatine kinase (CK)-emia during pyrexia. Mild hypotonia was observed, but other physical and neurological findings were unremarkable. The serum CK level was normal at rest or normothermia. Open muscle biopsy was performed on the rectus femoris, and showed glycogen storage and complete lack of phosphorylase activity histochemically and biochemically, establishing the diagnosis of McArdle disease. The diagnosis of McArdle disease in early infancy is uncommon. Until this study there have been no reports of clinical symptoms or muscle biopsy findings for McArdle disease in early childhood. This disease must be considered when transient hyper-CKemia is observed in infants, even if glycogen storage is unremarkable as compared with adult cases.