RESUMEN
Glycogen storage disease (GSD) due to a deficient hepatic phosphorylase system defines a genetically heterogeneous group of disorders that mainly manifests in children. We investigated 45 unrelated children in whom a liver GSD VI or IX was suspected on the basis of clinical symptoms including hepatomegaly, increased serum transaminases, postprandial lactatemia and/or mild fasting hypoglycemia. Liver phosphorylase and phosphorylase b kinase activities studied in peripheral blood cells allowed to suspect diagnosis in 37 cases but was uninformative in 5. Sequencing of liver phosphorylase genes was useful to establish an accurate diagnosis. Causative mutations were found either in the PYGL (11 patients), PHKA2 (26 patients), PHKG2 (three patients) or in the PHKB (three patients) genes. Eleven novel disease causative mutations, five missense (p.N188K, p.D228Y, p.P382L, p.R491H, p.L500R) and six truncating mutations (c.501_502ins361pb, c.528+2T>C, c.856-29_c.1518+614del, c.1620+1G>C, p.E703del and c.2313-1G>T) were identified in the PYGL gene. Seventeen novel disease causative mutations, ten missense (p.A42P, p.Q95R, p.G131D, p.G131V, p.Q134R, p.G187R, p.G300V, p.G300A, p.C326Y, p.W820G) and seven truncating (c.537+5G>A, p.G396DfsX28, p.Q404X, p.N653X, p.L855PfsX87, and two large deletions) were identified in the PHKA2 gene. Four novel truncating mutations (p.R168X, p.Q287X, p.I268PfsX12 and c.272-1G>C) were identified in the PHKG2 gene and three (c.573_577del, p.R364X, c.2427+3A>G) in the PHKB gene. Patients with PHKG2 mutations evolved towards cirrhosis. Molecular analysis of GSD VI or IX genes allows to confirm diagnosis suspected on the basis of enzymatic analysis and to establish diagnosis and avoid liver biopsy when enzymatic studies are not informative in blood cells.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno/sangre , Enfermedad del Almacenamiento de Glucógeno/diagnóstico , Hígado/enzimología , Hígado/patología , Fosforilasa Quinasa/deficiencia , Fosforilasas/deficiencia , Preescolar , Femenino , Estudios de Asociación Genética , Enfermedad del Almacenamiento de Glucógeno/enzimología , Enfermedad del Almacenamiento de Glucógeno/genética , Humanos , Lactante , Masculino , Mutación/genética , Fosforilasa Quinasa/genética , Fosforilasas/genéticaAsunto(s)
Hiperplasia Nodular Focal/etiología , Hiperplasia Nodular Focal/patología , Enfermedad del Almacenamiento de Glucógeno Tipo VI/complicaciones , Adolescente , Biopsia con Aguja , Femenino , Hiperplasia Nodular Focal/cirugía , Estudios de Seguimiento , Enfermedad del Almacenamiento de Glucógeno Tipo VI/diagnóstico , Humanos , Inmunohistoquímica , Monitoreo Fisiológico , Fosforilasas/deficiencia , Medición de Riesgo , Factores de TiempoRESUMEN
Myophosphorylase deficiency, or McArdle disease, is an uncommon entity. The gene for human myophosphorylase has been cloned and is located on chromosome 11, in keeping with the autosomal recessive nature of the disease and there is an excess of male patients. The diagnosis is established by documentation of elevated glycogen content and reduced phosphorylase activity in biopsied muscle tissue. We report four cases with McArdle disease which were 16, 15, 11 and 5 years old. They were brothers, and they came to the hospital because of pain, cramps and myoglobinuria after exercise or infection; in the first case, a male patient, myoglobinuria caused acute renal failure. Three of them showed reduced phosphorylase activity in biopsied muscle tissue. We discuss the different therapeutic possibilities.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Adolescente , Niño , Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Humanos , Masculino , Fosforilasas/deficienciaRESUMEN
OBJECTIVES: To investigate the clinical presentation, histological findings, and outcome of patients with congenital and metabolic myopathies (CM and MM) in whom the disease was diagnosed in childhood or adulthood. PATIENTS AND METHODS: We reviewed the diagnosis of all skeletal muscle biopsies performed by our group between 1984 and 1996 (13 years). All patients with CM and MM of childhood or adult onset were included in the study. Patients with mitochondrial myopathies were excluded because they are multisystemic disorders with a more distinct picture than that observed in other MM. We retrospectively reviewed the clinical history, with special emphasis on the clinical patterns of presentation, histological findings, and outcome. RESULTS: Among 1,865 biopsies, 28 (1.5%) fulfilled the diagnostic criteria for CM (seven nemaline myopathies, four multicore myopathies, three centronuclear myopathies) or MM (five adult-onset acid maltase deficiency, three myophosphorylase deficiency, three phosphofructokinase deficiency, two carnitine palmitoyl transferase deficiency, and one carnitine deficiency). In nearly half of the patients, mild stable weakness was the major complaint, whereas in one third muscular symptoms were intermittent and related to exercise. In a small number of cases, a persistently raised serum creatine kinase in an asymptomatic patient was the reason for muscle biopsy. Histological examination of skeletal muscle was highly indicative of a specific muscle disease in 26 of the 28 cases. After a mean follow-up of 7 years, the outcome has generally been good, and in most patients the myopathy did not worsen, most remaining ambulatory. CONCLUSION: CM and MM presenting in childhood or adulthood are infrequent; the symptoms are usually mild or moderate, and the prognosis generally is good.
Asunto(s)
Músculo Esquelético/patología , Trastornos Musculares Atróficos/patología , Miopatías Nemalínicas/patología , Adolescente , Adulto , Edad de Inicio , Anciano , Biopsia , Carnitina/deficiencia , Carnitina O-Palmitoiltransferasa/deficiencia , Niño , Preescolar , Creatina Quinasa/sangre , Femenino , Estudios de Seguimiento , Enfermedad del Almacenamiento de Glucógeno Tipo VII/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo VII/patología , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fibras Musculares Esqueléticas/enzimología , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/ultraestructura , Músculo Esquelético/enzimología , Trastornos Musculares Atróficos/congénito , Trastornos Musculares Atróficos/metabolismo , Miopatías Nemalínicas/metabolismo , Fosforilasas/deficiencia , Pronóstico , Recuperación de la Función , Estudios Retrospectivos , alfa-Glucosidasas/deficienciaAsunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/terapia , Creatina/uso terapéutico , Dietoterapia , Metabolismo Energético , Tolerancia al Ejercicio , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo V/metabolismo , Humanos , Fosforilasas/deficiencia , Piridoxina/uso terapéuticoRESUMEN
An asymptomatic 13-year-old boy, who never complained of exercise intolerance or myalgia, was found to have markedly elevated serum creatine kinase (CK) levels during a routine check-up. General physical and neurologic examinations were normal. Surprisingly, histochemical and biochemical analysis of muscle showed myophosphorylase deficiency and genetic analysis showed that the patient was homozygous for the most common mutation encountered in McArdle's disease (R49X). This case illustrates the fuzzy correlation between molecular defect and clinical phenotype in patients with McArdle's disease, and suggests that a thorough study of the muscle biopsy is important in patients with idiopathic hyperCKemia for correct diagnosis and careful follow-up.
Asunto(s)
Creatina Quinasa/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Adolescente , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Humanos , Masculino , Fosforilasas/deficienciaRESUMEN
OBJECTIVE: To investigate the degree of genetic heterogeneity of myophosphorylase deficiency (McArdle disease) in Spain through molecular studies of 10 new patients. DESIGN: The coding sequence of the entire myophosphorylase gene was sequenced in DNA extracted from muscle and blood. Restriction fragment length polymorphism analysis of polymerase chain reaction fragments was used to confirm and simplify detection of a novel mutation. SETTING: A collaborative study between 2 university laboratories in Spain and the United States. RESULTS: Five of the 10 patients harbored a novel missense mutation in exon 20, converting a tryptophan to an arginine (W797R). Three patients were homozygous for the "common" R49X mutation, and the remaining 2 patients were compound heterozygotes for R49X and a previously described missense mutation, G204S. CONCLUSIONS: The W797R missense mutation is the third novel mutation to be identified among Spanish patients. Its relative frequency suggests that it should be added to the R49X mutation in the molecular screening of McArdle disease in Spain.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Mutación Missense/genética , Fosforilasas/genética , Adulto , Sustitución de Aminoácidos , ADN/análisis , ADN/genética , Exones/genética , Femenino , Humanos , Masculino , Músculo Esquelético/enzimología , Fosforilasas/sangre , Fosforilasas/deficiencia , Reacción en Cadena de la Polimerasa , EspañaRESUMEN
The glycogen storage diseases are caused by inherited deficiencies of enzymes that regulate the synthesis or degradation of glycogen. In the past decade, considerable progress has been made in identifying the precise genetic abnormalities that cause the specific impairments of enzyme function. Likewise, improved understanding of the pathophysiologic derangements resulting from individual enzyme defects has led to the development of effective nutritional therapies for each of these disorders. Meticulous adherence to dietary therapy prevents hypoglycemia, ameliorates the biochemical abnormalities, decreases the size of the liver, and results in normal or nearly normal physical growth and development. Nevertheless, serious long-term complications, including nephropathy that can cause renal failure and hepatic adenomata that can become malignant, are a major concern in GSD-I. In GSD-III, the risk for hypoglycemia diminishes with age, and the liver decreases in size during puberty. Cirrhosis develops in some adult patients, and progressive myopathy and cardiomyopathy occur in patients with absent GDE activity in muscle. It remains unclear whether these complications of glycogen storage disease can be prevented by dietary therapy. Glycogen storage diseases caused by lack of phosphorylase activity are milder disorders with a good prognosis. The liver decreases in size, and biochemical abnormalities disappear by puberty.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/terapia , Sistema de la Enzima Desramificadora del Glucógeno/deficiencia , Sistema de la Enzima Desramificadora del Glucógeno/genética , Enfermedad del Almacenamiento de Glucógeno/genética , Enfermedad del Almacenamiento de Glucógeno/metabolismo , Enfermedad del Almacenamiento de Glucógeno/terapia , Glucógeno Sintasa/deficiencia , Glucógeno Sintasa/genética , Humanos , Fenotipo , Fosforilasa Quinasa/deficiencia , Fosforilasa Quinasa/genética , Fosforilasas/deficiencia , Fosforilasas/genéticaRESUMEN
We have studied two large unrelated Finnish families with myophosphorylase deficiency (McArdle's disease). In one, we identified a new nonsense mutation at codon 540 in exon 14 of the myophosphorylase gene, changing an encoded glutamic acid to a stop codon (E540X). The second family carried a splice-junction mutation at the 5' splice site of intron 14 (1844+G-->A), previously reported in one Caucasian patient and in a consanguineous Druze family. These data further enlarge the list of mutations associated with McArdle's disease and establish that McArdle's disease is genetically heterogeneous also within the Finnish population.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Adulto , Codón sin Sentido , ADN/genética , Femenino , Finlandia , Enfermedad del Almacenamiento de Glucógeno Tipo V/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Humanos , Músculo Esquelético/patología , Mutación , Linaje , Fosforilasas/deficiencia , Fosforilasas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trans-EmpalmeAsunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Protaminas/efectos adversos , Edema Pulmonar/inducido químicamente , Rabdomiólisis/inducido químicamente , Puente Cardiopulmonar/efectos adversos , Preescolar , Fiebre/etiología , Humanos , Masculino , Músculo Esquelético/enzimología , Fosforilasas/deficiencia , Tetralogía de Fallot/cirugíaAsunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Polimiositis/diagnóstico , Edad de Inicio , Biopsia , Creatina Quinasa/sangre , Diagnóstico Diferencial , Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Fosforilasas/deficiencia , Polimiositis/complicacionesRESUMEN
We identified a new mutation in the myophosphorylase gene in a Japanese family with McArdle's disease. This point mutation results in the replacement of a tryptophan at amino acid position 361 with a stop codon, the third nonsense mutation in this disorder. Our findings further expand the already wide spectrum of genetic lesions associated with McArdle's disease, and establish that molecular genetic heterogeneity is also present in the Japanese population.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Mutación Missense/genética , Fosforilasas/genética , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Biología Molecular , Linaje , Fosforilasas/deficiencia , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Terapia Genética , Enfermedades Musculares/genética , Enfermedades Musculares/terapia , Adenoviridae , Animales , Proteínas del Citoesqueleto/deficiencia , Proteínas del Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , ADN/administración & dosificación , Distroglicanos , Distrofina/deficiencia , Vectores Genéticos , Humanos , Glicoproteínas de Membrana/deficiencia , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/metabolismo , Músculos/anatomía & histología , Fosforilasas/deficiencia , Sarcoglicanos , Tibia/anatomía & histología , Regulación hacia Arriba , UtrofinaRESUMEN
We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.
Asunto(s)
Distrofias Musculares/genética , Fosforilasas/deficiencia , Adulto , Prueba de Esfuerzo , Humanos , Ácido Láctico/sangre , Masculino , Músculo Esquelético/patología , Distrofias Musculares/enzimología , Linaje , Fosforilasas/metabolismoRESUMEN
Our knowledge of the mechanisms leading to exercise intolerance is constantly expanding. Since the discovery of the glycolysis pathway block caused by phosphorylase deficiency as the cause of McArdle's disease, several other glycolysis blocks have been identified constituting a first group of exercise intolerance syndromes. A second group involves mitochondrial anomalies. More recently diverse exercise intolerance syndromes have been associated with insufficient regulation of calcium flow through the sarcoplasmic reticulum, particularly in sporadic cases of malignant hyperthermia with or without hyperthermia. A discrete form of dystrophinopathy is expressed by exercise-induced myalgia with myoglobinuria. Proximal myotonic myopathy also produces pain at exercise. The specificity of other syndromes such as AMP deaminase deficiency or myopathy with tubular aggregates remains debatable. Our understanding of these different syndromes, and their recognized or yet to be elucidated causes, is of practical significance for developing exploration protocols for patients with exercise intolerance with or without myoglobulinuria.
Asunto(s)
Ejercicio Físico , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Resistencia Física , Aptitud Física , Femenino , Humanos , Masculino , Fosforilasas/deficiencia , Esfuerzo FísicoRESUMEN
OBJECTIVES: The aim of the study was to evaluate the biochemical causes of recurrent rhabdomyolysis in Finland. MATERIAL AND METHODS: We examined 22 patients with recurrent rhabdomyolysis, and 26 patients with one episode of rhabdomyolysis or other symptoms compatible with metabolic myopathy. Muscle histopathology and activities of phosphorylase (PHRL) (total and active), phosphofructokinase (PFK), carnitine palmitoyltransferase (CPT) and myoadenylate deaminase (MAD) were studied. The limit of enzyme deficiency was defined as enzyme activity less than 5% of the mean of the control subjects. RESULTS: We found 4 patients with muscle PHRL deficiency, 1 patient with PFK deficiency and 1 patient with evidence of phosphorylase kinase deficiency. One patient had Becker's muscle dystrophy, 2 patients had unspecified dystrophies, 1 patient had Miyoshi myopathy, and 1 patient had a form of mitochondrial encephalomyopathy (MELAS). CONCLUSION: Enzyme defects were found in 23% of the patients with recurrent rhabdomyolysis. Other muscle diseases, muscular dystrophies or myopathies, were detected in 18% of these patients, emphasizing the value of clinical and histopathological examination of patients with previous rhabdomyolysis.
Asunto(s)
Músculo Esquelético/enzimología , Rabdomiólisis/enzimología , AMP Desaminasa/biosíntesis , Adolescente , Adulto , Biopsia , Carnitina O-Palmitoiltransferasa/biosíntesis , Carnitina O-Palmitoiltransferasa/deficiencia , Creatina Quinasa/sangre , Ejercicio Físico/fisiología , Prueba de Esfuerzo , Femenino , Antebrazo/irrigación sanguínea , Humanos , Isquemia/sangre , Isquemia/diagnóstico , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Fosfofructoquinasa-1/biosíntesis , Fosforilasa Quinasa/biosíntesis , Fosforilasa Quinasa/deficiencia , Fosforilasas/biosíntesis , Fosforilasas/deficiencia , Recurrencia , Rabdomiólisis/etiología , Rabdomiólisis/patologíaRESUMEN
Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.
Asunto(s)
Acidosis/fisiopatología , Ejercicio Físico/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Estudios de Casos y Controles , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Miopatías Mitocondriales/fisiopatología , Contracción Muscular/fisiología , Fosfatos/sangre , Fosfofructoquinasa-1/deficiencia , Fosforilasas/deficienciaRESUMEN
OBJECTIVE: To develop a simple test for the determination of genetic susceptibility to myophosphorylase deficiency in Charolais cattle. ANIMALS: 48 adult Charolais cattle and 233 calves from one herd and 3 Charolais cattle from 2 other herds. Sixty Piedmontese and 34 Saler cattle provided negative-control samples. PROCEDURE: Cattle were from a Charolais herd in which myophosphorylase deficiency was identified and 2 other herds in which cattle had signs compatible with the disease. Genomic DNA was isolated from heparinized blood samples. A segment of the myophosphorylase gene containing the mutation site was amplified by polymerase chain reaction assays, and the genotype (normal vs affected allele) was determined by using restriction enzyme and agarose gel electrophoretic analysis. RESULTS: The 3 myophosphorylase genotypes (homozygous normal, homozygous affected, and heterozygous) could be readily identified. Segregation of the affected allele could be determined in an extended pedigree, and all clinically affected cattle were homozygous for this allele. Determination of the distribution of normal and affected alleles in a large population did not indicate a strong selective advantage for heterozygous carriers in this herd. Heterozygotes were also identified in Charolais cattle from the 2 other herds. CONCLUSIONS: Breeders of Charolais cattle can use this genetic test to perform marker-assisted selection and remove cattle with the mutant myophosphorylase allele from the breeding population. Alternatively, they could more accurately determine selective advantages and disadvantages for cattle with the affected allele. CLINICAL RELEVANCE: Development of this test enables rapid genetic screening of Charolais and related breeds of cattle for detection of the mutation responsible for myophosphorylase deficiency.
Asunto(s)
Bovinos/genética , Fosforilasas/deficiencia , Fosforilasas/genética , Mutación Puntual , Animales , Secuencia de Bases , Codón , ADN/sangre , Exones , Femenino , Genotipo , Intrones , Masculino , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la Polimerasa/métodos , Especificidad de la EspecieRESUMEN
We studied a 21-year-old patient with clinical, biochemical and histochemical evidence of myophosphorylase deficiency and unusual repetitive episodes of pigmenturia. His muscle biopsy also revealed morphological signs of mitochondrial proliferation and a defect of complex I of the respiratory chain. His mother had exercise intolerance without myoglobinuria and no histochemical evidence of myophosphorylase deficiency. In muscle, the mother showed some ragged-red fibers, normal respiratory chain levels and a significant residual phosphorylase activity. Molecular genetic analysis revealed that the proband was homozygous for the mutation commonly found in McArdle's disease. The mother, father, and the five siblings were all heterozygous for the same mutation. Mitochondrial DNA analysis of the proband's muscle failed to demonstrate known mutations associated with his clinical pattern. Moreover, we sequenced his tRNA(Leu(UUR)) gene, a hot spot for mutations, showing no abnormality.
Asunto(s)
Codón sin Sentido , Transporte de Electrón , Homocigoto , Mitocondrias Musculares/enzimología , NAD(P)H Deshidrogenasa (Quinona)/genética , Fosforilasas/deficiencia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , LinajeRESUMEN
McArdle's disease (glycogenosis type V) is a metabolic disorder of hydrocarbons, inherited with autosomic recessive pattern. Biochemically is defined by a myophosphorylase deficiency; clinically it is characterized by exercise intolerance, due to the impossibility of providing energetic substrate to the muscle, myalgias and stiffness. We present a case report of a patient with McArdle's disease and we comment the diagnostic procedures and current therapeutic options.