Handbook of Genetic Counseling/Short Chain Acyl-CoA Dehydrogenase (SCAD)

Short Chain Acyl-CoA Dehydrogenase (SCAD) General Information a disorder of lipid metabolism characterized by a defect in the oxidation of short-chain fatty acids resulting in neurologic and gastrointestinal manifestations SCAD is one of four enzymes in the mitochondria responsible for the breakdown of short-chain (C4-C6) fatty acids to 2-carbon fragments (acetyl-CoA) in the beta oxidation pathway homozygous patients are unable to mobilize large fat stores and are thus at risk for becoming hypoglycemic when stressed (i.e., during infection or fasting) during which time the long and medium acyl-CoA dehydrogenases are unable to compensate for the lack of SCAD gene map locus: 12q22-qter autosomal recessive inheritance Diagnosis diagnosis is difficult because patients do not consistently excrete characteristic metabolites it is necessary to collect and analyze several urine and plasma specimens in patients with neurologic abnormalities that suggest this disorder deficiency of SCAD activity in leukocytes and cultured skin fibroblasts prenatally, a deficiency of SCAD activity in cultured chorionic villi or amniocytes can be detected Clinical Evaluation two distinct clinical phenotypes have been identified : one type observed in infants with acute acidosis and muscle weakness (generalized) one type observed in middle-aged patients with chronic myopathy (localized to skeletal muscles) cases with neonatal onset have a variable phenotype includes metabolic acidosis, failure to thrive, developmental delay, seizures and myopathy no episodes of nonketotic hypoglycemia (characteristic of medium-chain and long-chain acyl dehydrogenase deficiencies) Infantile type metabolic: neonatal acidosis, low-normal plasma total carnitine, highly esterified GI: poor feeding, vomiting, failure to thrive muscle: progressive skeletal muscle weakness, hypotonia neurological: developmental delay laboratory results: generalized SCAD deficiency, ethylmalonate urinary excretion, low normal highly esterified muscle carnitine Adult type muscle: lipid-storage myopathy lab results: skeletal muscle carnitine low, deficiency of skeletal muscle mitochondrial short-chain acyl-CoA (butyryl-CoA) Support Groups James William Lazzaro Foundation 4493 Liberty Road South Euclid, OH 44121 Contact Person: Jamie Lazzaro Phone: (502) 254-2209 Email: info@jwlsite.com Website: www.jwlsite.com FOD(Fatty Oxidation Disorders)Family Support Group 2041 Tomahawk Okemos, MI 48864 Contact Person: Deb Lee Gould, MEd Phone: (517) 381-1940 Email: deb@fodsupport.org Website: www.fodsupport.org Sources Bhala A, Willi SM, Rinaldo P, Bennett MJ, Schmidt-Sommerfeld E, Hale DE. "Clinical and biochemical characterization of short-chain acyl-coenzyme A dehydrogenase deficiency." J Pediatr 1995 Jun;126(6):910-5 OMIM Notes The information in this outline was last updated in 2002/