Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate the clinical and neurophysiologic responses to oral prednisone therapy in a boy with enzymatically confirmed long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency in biopsied muscle and cultured skin fibroblasts. This boy presented with progressive limb girdle myopathy, recurrent myoglobinuria, peripheral sensorimotor axonopathy, and intraventricular conduction delays. Prior to prednisone therapy, at age 8 years, he exhibited marked distal weakness greater than proximal weakness with a waddling and high-steppage gait, Gowers' maneuver (10 s to rise from the floor), fatigue after 3-20 yards of walking and the ability to climb only 2 stairs. Serum levels of creatine kinase rose from 34 to 4,124 U/L following mild exertion. Nerve conduction studies revealed progressive axonopathy with secondary demyelination. Four weeks after initiation of oral prednisone (0.75 mg/kg/day) therapy, there was approximately a 100% increase in power and endurance. He was able to walk at least 100 yards before tiring, could rise from sitting on the floor in 3-4 s, and was able to climb 20 steps in 30 s. There was concurrent improvement in nerve conduction studies. Prednisone was gradually withdrawn over the next 4 months to 0.19 mg/kg/day; lower doses of 0.08 mg/kg/day resulted in a marked deterioration in power to the prior state. Although 0.19 mg/kg/day did not maintain the peak power achieved at 0.75 mg/kg/day, it provided adequate baseline power and endurance. It is concluded that there was a significant clinical and neurophysiologic response to prednisone at a dosage > or = 0.16 mg/kg/day. Prednisone may stabilize muscle and neuronal plasma membranes, as well as the fatty acid oxidation enzyme complex in the mitochondrial membrane.
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PMID:Clinical and neurophysiologic response of myopathy and neuropathy in long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency to oral prednisone. 774 66

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