Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the discovery in 1959 of myophosphorylase deficiency, at least 15 myopathies due to deficiency of enzymes involved in energy substrate utilization have been described. In this review two main categories of enzymopathies, glycogenosis and mitochondrial disorders, are discussed. Clinically, the patients with these categories of enzyme defects present two major syndromes: acute recurrent muscle impairment, generally related to exercise, associated with cramps and/or myoglobinuria; progressive muscular weakness and wasting eventually associated with signs of affected organs other than skeletal muscle. Defects of glycogen breakdown and of the first step of glycolysis are more frequently associated with acute exercise intolerance, such as in myophosphorylase and phosphofructokinase deficiencies, but may be associated with progressive muscle weakness and wasting, such as in acid maltase and debrancher enzyme deficiency. Clinical heterogeneity is common in these disorders, but a biochemical explanation for their different clinical expression is still lacking. Defects of the second step of glycolysis, phosphoglycerate kinase, phosphoglycerate mutase and lactate dehydrogenase deficiencies, have been discovered recently and are associated with exercise intolerance. The reason for muscle weakness and atrophy in glycogenosis is still unclear, although it has been suggested that excessive protein catabolism occurs in myophosphorylase, debrancher and acid maltase deficiencies. Myopathies due to deficiencies of mitochondrial enzymes are less well defined, as a group, than the glycogenoses. They are currently considered to fall into three main groups: defects of substrate utilization, such as carnitine palmitoyltransferase deficiency; defects of respiratory chain complexes, such as cytochrome-c-oxidase deficiency and defects of phosphorylation-respiration coupling, such as Luft's disease. Again, severe and benign exercise intolerance or progressive life-threatening myopathic syndromes may be the clinical expression of these disorders. Detailed biochemical and morphological studies of muscle biopsies are needed in these patients to obtain a definite diagnosis and prognosis, and to decide on eventual treatment.
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PMID:Myopathies due to enzyme deficiencies. 293 18

Adult patients with metabolic myopathies typically present with exercise-induced pain, cramps, fatigue, and myoglobinuria. The current therapeutic options of glycogen and lipid storage myopathies include dietary treatments, excersise training, and pharmacological supplementations. Herein is a review of evidence from randomized controlled trials in McArdle disease (glycogen storage disease type V, muscle phosphorylase deficiency) and carnitine palmitoyltransferase (CPT) 2 deficiency. A brief overview on current treatment options in rhabdomyolysis is also included because patients with McArdle disease and CPT 2 often experience such potentially life-threatening complications.
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PMID:Therapeutic options in other metabolic myopathies. 1901 9

Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). Fig. 1 Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK-creatine kinase; COX-cytochrome c oxidase; CPT-carnitine palmitoyl transferase; cyt b-cytochrome b; mtDNA-mitochondrial DNA; nDNA-nuclear DNA; PFK-phosphofructokinase; PGAM-phosphoglycerate mutase; PGK-phosphoglycerate kinase; PPL-myophosphorylase; RRF-ragged red fibers; TFP-trifunctional protein deficiency; VLCAD-very long-chain acyl-coenzyme A dehydrogenase.
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PMID:A diagnostic algorithm for metabolic myopathies. 2042 36