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Acylated coenzyme A (acyl-CoA) dehydrogenases are a family of mitochondrial enzymes that catalyze the first dehydrogenation step in the beta oxidation of fatty acyl-CoA derivatives. Fatty acids provide important respiratory fuel for many tissues, including heart, brain, skeletal muscle, pancreas, placenta, brown adipose tissue, kidney, and liver. The disorder is inherited as an autosomal recessive trait. Metabolic acidosis, severe hypoglycemia without ketosis, and coma are frequent features of all types of acyl-CoA dehydrogenase deficiency syndrome. It also occurs during adulthood. Large amounts of glutaric acid in the blood and urine are caused by deficiency of the enzyme “multiple acyl-CoA dehydrogenase".

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The family of acyl-CoA dehydrogenase deficiency syndromes contains eight members. The most frequent are the following five:

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  • Short-chain acyl-CoA dehydrogenase deficiency (SCAD)
  • Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
  • Long-chain acyl-CoA dehydrogenase deficiency (LCAD)
  • Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
  • Multiple acyl-CoA dehydrogenase deficiency (MADD)(Synonym: Glutaric Acidemia Type II)

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All types are inherited as either autosomal dominant or recessive pattern.

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All acyl-CoA dehydrogenase deficiencies catalyze the same initial dehydrogenation of the substrate at the beta-carbon atom and require electron transfer flavoprotein as an electron acceptor. They differ distinctly from each other with regard to the length and configuration of the hydrocarbon chain of their respective substrates and have accordingly received appropriate names. They are nuclear encoded and are synthesized as precursor proteins in the cytosol with an N-terminal leader peptide, which is cleaved off upon import to the mitochondria, producing a mature monomer. It has been genetically mapped on the 11q25. Analysis using a Northern blot system detected an approximately 2.1-kb ACAD8 transcript in all tissues examined, namely, heart, lung, brain, skeletal muscle, pancreas, placenta, liver, and kidney.

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Short-chain acyl-CoA dehydrogenase deficiency (SCAD) is an extremely rare inherited disorder of fat metabolism often recognized as an organic acidemia disorder. All reported cases have occurred in females. A pattern of occurrence has not been defined. Severe metabolic acidosis and hyperammonemia are principal features of the disorder. There are two distinct types of SCAD. A congenital form is characterized by progressive hypotonia and organic acidemia. The clinical symptoms in infants associated with organic acidemia include poor feeding, frequent vomiting, failure to thrive, progressive muscle weakness, hypotonia, growth retardation, impaired mental development, and lethargy. Other features may include hypoglycemia, accumulation of excessive amounts of fatty acids in muscle and/or liver tissue, and severe hyperammonemia. Unusually low levels of carnitine in muscle tissue (secondary carnitine deficiency) may occur. In some infants the presence of cerebral edema and raised intracranial pressure, hepatosplenomegaly, liver steatosis, biliary cholestasis, and focal hepatocellular necrosis have been reported. It often is considered life-threatening. The milder adult onset form of this disorder affects the skeletal muscles and is characterized by severe muscle weakness. Muscle weakness probably is the result of accumulation of fatty acids leading to lipid storage myopathy. An abnormally low levels of the amino acid ...

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