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

Disorders of glycogen, lipid or mitochondrial metabolism may cause two main clinical syndromes, namely (1) progressive weakness (eg, acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; long- and very-long-chain acyl-CoA dehydrogenase (LCAD, VLCAD), and trifunctional enzyme deficiencies among the fatty acid oxidation (FAO) defects; and mitochondrial enzyme deficiencies) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps) (eg, phosphorylase (PPL), phosphorylase b kinase (PBK), phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), and lactate dehydrogenase (LDH) among the glycogenoses and carnitine palmitoyltransferase II (CPT II) deficiency among the disorders of FAO or (3) both (eg, PPL, PBK, PFK among the glycogenoses; LCAD, VLCAD, short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD), and trifunctional enzyme deficiencies among the FAO defects; and multiple mitochondrial DNA (mtDNA) deletions). Myoadenylate deaminase deficiency, a purine nucleotide cycle defect, is somewhat controversial and is characterized by exercise-related cramps leading rarely to myoglobinuria.
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PMID:Metabolic myopathies. 879 43

The primary presentations of neuromuscular disease in the newborn period are hypotonia and weakness. Although metabolic myopathies are inherited disorders that present from birth and may present with subtle to marked neonatal hypotonia, a number of these defects are diagnosed classically in childhood, adolescence, or adulthood. Disorders of glycogen, lipid, or mitochondrial metabolism may cause three main clinical syndromes in muscle, namely, (1) progressive weakness with hypotonia (e.g., acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; carnitine uptake and carnitine acylcarnitine translocase defects among the fatty acid oxidation (FAO) defects; and cytochrome oxidase deficiency among the mitochondrial disorders) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps), e.g., phosphorylase, phosphofructokinase, and phosphoglycerate kinase among the glycogenoses and carnitine palmitoyltransferase II deficiency among the disorders of FAO or (3) both (e.g., long-chain or very long-chain acyl coenzyme A (CoA) dehydrogenase, short-chain L-3-hydroxyacyl-CoA dehydrogenase, and trifunctional protein deficiencies among the FAO defects). Episodes of exercise-induced myoglobinuria tend to present in later childhood or adolescence; however, myoglobinuria in the first year of life may occur in FAO disorders during catabolic crises precipitated by fasting or infection. The following is a survey of genetic disorders of glycogen and lipid metabolism resulting in myopathy, focusing primarily on those defects, to date, that have presented in the neonatal or early infancy period. Disorders of mitochondrial metabolism are discussed in another chapter.
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PMID:Neonatal metabolic myopathies. 1033 65