Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.1.8 (acyl-CoA dehydrogenase)
 785 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acyl-CoA dehydrogenases are a family of multimeric flavoenzymes that catalyze the alpha,beta -dehydrogenation of acyl-CoA esters in fatty acid beta -oxidation and amino acid catabolism. Genetic defects have been identified in most of the acyl-CoA dehydrogenases in humans. Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified acyl-CoA dehydrogenase that demonstrates maximum activity with unsaturated long-chain acyl-CoAs. We now report three cases of ACAD9 deficiency. Patient 1 was a 14-year-old, previously healthy boy who died of a Reye-like episode and cerebellar stroke triggered by a mild viral illness and ingestion of aspirin. Patient 2 was a 10-year-old girl who first presented at age 4 mo with recurrent episodes of acute liver dysfunction and hypoglycemia, with otherwise minor illnesses. Patient 3 was a 4.5-year-old girl who died of cardiomyopathy and whose sibling also died of cardiomyopathy at age 21 mo. Mild chronic neurologic dysfunction was reported in all three patients. Defects in ACAD9 mRNA were identified in the first two patients, and all patients manifested marked defects in ACAD9 protein. Despite a significant overlap of substrate specificity, it appears that ACAD9 and very-long-chain acyl-CoA dehydrogenase are unable to compensate for each other in patients with either deficiency. Studies of the tissue distribution and gene regulation of ACAD9 and very-long-chain acyl-CoA dehydrogenase identify the presence of two independently regulated functional pathways for long-chain fat metabolism, indicating that these two enzymes are likely to be involved in different physiological functions.
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PMID:A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency. 1756 66

Despite recent advances in the elucidation of etiology and pathogenesis of mitochondrial disorders, their therapeutic management remains challenging. This review focuses on currently available therapeutic options for human mitochondrial disorders. Current treatment of mitochondrial disorders relies on symptomatic, multidisciplinary therapies of various manifestations in organs such as the brain, muscle, nerves, eyes, ears, endocrine organs, heart, intestines, kidneys, lungs, bones, bone marrow, cartilage, immune system, and skin. If respiratory chain functions are primarily or secondarily impaired, antioxidants or cofactors should be additionally given one by one. All patients with mitochondrial disorders should be offered an individually tailored diet and physical training program. Irrespective of the pathogenesis, all patients with mitochondrial disorders should avoid exposure to mitochondrion-toxic agents and environments. Specific treatment can be offered for stroke-like episodes, mitochondrial epilepsy, mitochondrial neurogastrointestinal encephalopathy, Leber hereditary optic neuropathy, thiamine-responsive Leigh syndrome, primary coenzyme Q deficiency, primary carnitine deficiency, Friedreich ataxia, ethylmalonic encephalopathy, acyl-CoA dehydrogenase deficiency, pyruvate dehydrogenase deficiency, and hereditary vitamin E deficiency. Preventing the transmission of mitochondrial DNA-related mitochondrial disorders can be achieved by mitochondrion replacement therapy (spindle transfer, pronuclear transfer). In conclusion, specific and nonspecific therapies for human mitochondrial disorders are available, and beneficial effects have been anecdotally reported. However, double-blind, placebo-controlled studies to confirm effectiveness are lacking for the majority of the measures applied to mitochondrial disorders. Transmission of certain mitochondrial disorders can be prevented by mitochondrion replacement therapy. A multidisciplinary approach is required to meet the therapeutic challenges of patients with mitochondrial disorders.
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PMID:Clinical Therapeutic Management of Human Mitochondrial Disorders. 3305 53