Disease relevance of NSC 96615

• Defects in the SCAD enzyme are associated with failure to thrive, often with neuromuscular dysfunction and elevated urinary excretion of ethylmalonic acid (EMA) [1].
• Ethylmalonic encephalopathy (EE), an organic aciduria of unknown etiology characterized by developmental delay, hypotonia, and vascular instability associated with lactic acidemia and urinary excretion of ethylmalonic acid (EMA) and methylsuccinic acid (MSA), has been described in 11 patients [2].
• EE is a devastating infantile metabolic disorder, characterised by widespread lesions in the brain, hyperlactic acidaemia, petechiae, orthostatic acrocyanosis, and high levels of ethylmalonic acid in body fluids [3].
• MAIN OUTCOME MEASURES: Prevalence, genotype (mutation/mutation, mutation/variant, variant/variant), C4-C and EMA levels, clinical signs and symptoms, and clinical course [4].

Psychiatry related information on NSC 96615

• CONCLUSIONS: The low triiodothyronine concentrations observed in anorexia nervosa could alter the extent of riboflavin conversion into cofactors, thus leading to high erythrocyte riboflavin concentrations, low plasma flavin adenine dinucleotide concentrations, and high rates of ethylmalonic acid and isovalerylglycine excretion [5].

High impact information on NSC 96615

• High levels of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase activity is decreased in skeletal muscle [6].
• We have shown previously that a variant allele of the short-chain acyl-CoA dehydrogenase ( SCAD ) gene, 625G-->A, is present in homozygous form in 7% of control individuals and in 60% of 135 patients with elevated urinary excretion of ethylmalonic acid (EMA) [7].
• One hundred and thirty-five patients from Germany, Denmark, the Czech Republic, Spain, and the United States were selected for this study on the basis of abnormal EMA excretion ranging from 18 to 1185 mmol/mol of creatinine (controls < 18 mmol/mol of creatinine) [8].
• Gas chromatography and mass spectrometry of urine revealed that ethylmalonic acid was present in all samples but not always at elevated concentrations; methylsuccinic acid and butyrylglycine were sporadically elevated. n-Butyrylcarnitine was often found in urine and plasma [9].
• A child is reported presenting with a clinical picture suggestive of genetic connective tissue disorders (vascular fragility, articular hyperlaxity, delayed motor development, and normal cognitive development), an absence of pathological ethylmalonic acid excretion during inter-critical phases and a homozygous R163W mutation in the ETHE1 gene [10].

Biological context of NSC 96615

• Effect of in vivo administration of ethylmalonic acid on energy metabolism in rat tissues [11].
• Inhibition of the electron transport chain and creatine kinase activity by ethylmalonic acid in human skeletal muscle [12].

Anatomical context of NSC 96615

• Inhibition of creatine kinase activity in vitro by ethylmalonic acid in cerebral cortex of young rats [13].
• STUDY DESIGN: We studied a family with SCAD deficiency and determined urinary ethylmalonic acid excretion, plasma C(4)-carnitine, SCAD enzyme activity in fibroblasts and lymphocytes, DNA mutations in the SCAD gene, and clinical expression [14].

Gene context of NSC 96615

• Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of predominantly ethylmalonic acid (EMA) and clinically by neurological dysfunction [15].
• Metabolic screening was performed during a hospitalization at 8 years of age and revealed an increased excretion of ethylmalonic acid (EMA; 45-80 mmol/mol creatinine, normal 0.2-6.6), suggesting a degradation defect of short-chain fatty acids [16].
• The urinary excretion of ethylmalonic acid was studied in various patients, including children with glutaric aciduria type II and with beta-ketothiolase deficiency [17].

References