1/22. A missense mutation W797R in the myophosphorylase gene in a Spanish patient with McArdle's disease.We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous T-to-C transition results in the replacement of a highly conserved tryptophan at amino acid position (aa) 797 with an arginine in the C-terminal domain of the PYGM protein. The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the aa 797 in the normal function of the PYGM protein. Our data further expand the genetic heterogeneity in patients with McArdle's disease.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/22. Myophosphorylase deficiency (McArdle's disease): report of a family.The clinical and biochemical findings are presented of two brothers suffering from McArdle's Disease (Myophosphorylase Deficiency). Tissue enzyme estimations and lactate levels were done in affected and non-affected members of the family. Affected members showed absence of phosphorylase enzyme by histochemical and quantitative estimation. No quantitative abnormalities were found in other enzyme systems of glycolytic pathways in the family investigated. Various other aspects of clinical features, biochemical abnormalities and inheritance are discussed.- - - - - - - - - - ranking = 3keywords = enzyme (Clic here for more details about this article) |
3/22. McArdle's disease in childhood: report of a new case.McArdle's disease (glycogenosis type V) is an inherited glycogen storage disease characterized clinically by myalgia, cramps and sometimes myoglobinuria, triggered by exercise. The onset of exercise intolerance is usually in late childhood or adolescence and diagnosis is exceptionally established during infancy. We report the case of a 6-year-old girl who had been complaining of aching muscles for a long time, and who presented after a near-drowning incident, with extensive muscle necrosis, probably secondary to myophosphorylase deficiency-induced cramps. These unusual manifestations led to the diagnosis of this rare disorder. We compare the clinical findings of this case to nine previous reports. This highlights the heterogeneous spectrum of this disease in childhood and supports the distinction of three clinical pictures in childhood: a neonatal form rapidly fatal, a milder form with congenital myopathic symptoms and a benign classical form with myalgia, cramps and pigmenturia.- - - - - - - - - - ranking = 1428.2597108651keywords = storage disease, storage (Clic here for more details about this article) |
4/22. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways.Inborn errors of metabolism show considerable variation in the severity of symptoms. This is often ascribed to the differential effects of specific mutations on gene/enzyme function; however, such genotype/phenotype correlations are usually imprecise. In addition, in some patients with clinical and biochemical findings consistent with a defect in a particular metabolic pathway, it is ultimately impossible to arrive at a precise enzymatic diagnosis. In this situation, we have increasingly been identifying concurrent partial defects in more than one pathway, or at multiple steps in one pathway. In this study, we present the clinical, biochemical, and molecular findings from several patients showing multiple partial defects in energy metabolism. These patients show clinical symptoms consistent with a defect in the affected pathways even though they do not have a complete deficiency in any one enzyme. We hypothesize that such patients are exhibiting clinically significant reductions in energy metabolism related to the compound effects of these partial defects, a phenomenon we term "synergistic heterozygosity." Based on the frequencies of known disorders of energy metabolism, we propose that this may represent a previously unrecognized, relatively common mechanism of disease of potentially great clinical relevance.- - - - - - - - - - ranking = 2keywords = enzyme (Clic here for more details about this article) |
5/22. adult-onset exercise intolerance due to phosphorylase b kinase deficiency.Muscle-specific phosphorylase b kinase deficiency is an unusual form of glycogen storage disorder. The majority of patients are male with an age at diagnosis between 15 to 36 years. Clinical features include exercise intolerance, myalgia and muscle weakness. A forearm ischaemic exercise test is usually normal and histochemical staining for myophosphorylase positive. The demonstration of reduced muscle phosphorylase b kinase activity by biochemical assay confirms the diagnosis.We report a 36 year old male with phosphorylase b kinase deficiency and symptom onset in adult life.- - - - - - - - - - ranking = 124.51845553324keywords = storage (Clic here for more details about this article) |
6/22. A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes.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.- - - - - - - - - - ranking = 249.03691106647keywords = storage (Clic here for more details about this article) |
7/22. In vivo 13C-NMR evaluation of glycogen content in a patient with glycogen storage disease.glycogen storage disease was suspected in a 10-month-old boy. Initial technical problems did not permit the determination of the precise enzyme, deficiency, and type VI glycogen storage disease was only diagnosed at the age of 2 years. In the mean time, natural abundance 13C nuclear magnetic resonance evaluation of muscular and hepatic glycogen content indicated normal muscular glycogen and increased hepatic glycogen in our patient, a finding which strongly argued for the diagnosis of type VI glycogen storage disease. Even though the use of nuclear magnetic resonance might seem, in this situation, a somewhat circuitous means of reaching the diagnosis, it appears that nuclear magnetic resonance could provide a useful tool for a non-invasive diagnosis of glycogen storage diseases.- - - - - - - - - - ranking = 11427.077686921keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
8/22. The case of stainless statins.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).- - - - - - - - - - ranking = 1428.2597108651keywords = storage disease, storage (Clic here for more details about this article) |
9/22. McArdle's disease presenting as unexplained dyspnea in a young woman.McArdle's disease is a rare, inherited deficiency of myophosphorylase, an enzyme required for the utilization of glycogen. patients with myophosphorylase deficiency classically present with exercise intolerance, leg pain and muscle fatigue. The case of a young woman with exertional dyspnea and leg cramps is described. Exercise testing confirmed the presence of exercise intolerance and demonstrated an accelerated heart rate response, despite the absence of an anaerobic threshold and a respiratory exchange ratio of less than 1.0. Subsequent ischemic forearm testing and muscle biopsy confirmed the diagnosis of myophosphorylase deficiency. Evaluation of lung mechanics with esophageal pressure measurements demonstrated the presence of respiratory muscle weakness and early fatiguability, suggesting that the patient's dyspnea might have been attributable to an increased respiratory effort. dyspnea is not a classic symptom associated with myophosphorylase deficiency, although subclinical respiratory muscle impairment may be present. No previous studies have evaluated respiratory muscle function during exercise in patients with myophosphorylase deficiency.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
10/22. McArdle's disease diagnosed following statin-induced myositis.We describe the case of a 69-year-old man with a history of muscular symptoms dating back to his childhood; McArdle's disease (glycogen-storage disease V) was diagnosed following an episode of myositis in which a statin and physical exertion appear to have been precipitating factors. This case demonstrates that the ischaemic lactate-ammonia test still has a place in screening patients with symptoms suggestive of McArdle's disease and emphasizes the importance of carrying out glycogen phosphorylase histochemistry on the skeletal muscle biopsy to confirm the diagnosis. In patients who develop a raised plasma creatine kinase level or muscular symptoms during lipid-lowering therapy, the clinician should be alert to the possibility of an underlying myopathy.- - - - - - - - - - ranking = 1428.2597108651keywords = storage disease, storage (Clic here for more details about this article) |
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