Information on the following diseases can be found in the Related Disorders section of this report:

• Medium-Chain Acyl-CoA Dehydrogenase Deficiency
• Long-Chain Acyl-CoA Dehydrogenase Deficiency
• Gluctaricaciduria II (GA IIA)
• Ornithine Transcarbamylase Deficiency
• Urea Cycle Enzyme Deficiencies (General)

The symptoms of SCAD are similar to those of other mitochondrial fatty acid oxidation disorders, but usually milder. Infants with SCAD may present with poor feeding habits, frequent vomiting, failure to thrive, progressive muscle weakness, loss of muscle tone (hypotonia), growth delays, impaired mental development, and/or lethargy. Other symptoms may include abnormally low levels of circulating glucose in the blood (hypoglycemia), accumulation of excessive amounts of fatty acids in muscle and/or liver tissue, and/or abnormally high levels of ammonia in the blood (hyperammonemia). Unusually low levels of carnitine, a substance necessary for mitochondrial fatty acid oxidation, in muscle tissue (secondary carnitine deficiency) may also occur.

Rarely, some infants with congenital SCAD show signs of abnormal fluid accumulation in the brain (cerebral edema), enlargement of the liver and spleen (hepatosplenomegaly), fatty changes in the liver, suppression of the flow of bile from the liver (cholestasis), and/or progressive loss of liver function (focal hepatocellular necrosis).
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Short-chain acyl-CoA dehydrogenase deficiency is an autosomal recessive disorder that appears to affect females only. The faulty gene has been tracked to Gene Map Locus 12q22-qter.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 12q22-qter" refers to a region between band 22 on the long arm of chromosome 12 and the end of that long arm (ter). The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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No propensity with regard to race or ethnicity has been detected.
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Symptoms of the following disorders can be similar to those of short-chain acyl-CoA dehydrogenase deficiency. Comparisons may be useful for a differential diagnosis:

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is another rare inherited metabolic disorder of fat metabolism (FOD). It is caused by a deficiency of the enzyme medium-chain CoA dehydrogenase. Symptoms usually include recurring acute episodes of high acidity in blood and body tissues (metabolic acidosis) and abnormally low blood glucose levels (hypoglycemia) after fasting. Fatigue and coma may also occur. The onset of symptoms may occur during infancy or early childhood. Fatty changes in the liver may also develop. The symptoms are similar to those of other fatty acid oxidation disorders. (For more information on this disorder, choose "Medium-Chain Acyl-CoA Dehydrogenase Deficiency" as your search term in the Rare Disease Database.)

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) is yet another rare inherited metabolic disorder of fat metabolism, or FOD. It affects infants and is caused by a deficiency of the enzyme known as very-long-chain CoA dehydrogenase. The symptoms of this disorder are similar to, but more severe than, those of medium-chain Acyl-CoA dehydrogenase deficiency (MCAD). Characteristic signs usually appear shortly after birth and include recurrent episodes of low blood glucose levels (hypoglycemia), vomiting, and/or coma after periods of low food consumption. Muscle weakness, heart disease due to enlargement of the muscles of the heart (hypertrophic cardiomyopathy), and/or an enlarged liver (hepatomegaly) may also occur. Other symptoms may include abnormally high levels of acids in the urine, abnormally low levels of the amino acid carnitine in muscle tissue (secondary carnitine deficiency), and/or abnormal liver function test results.

Glutaricaciduria II (GA II) is a rare inherited metabolic disorder that is a form of the organic acidemia. The more serious neonatal form (GA IIA) may or may not be associated with congenital abnormalities, and is characterized by large amounts of glutaric acid in blood and urine. Severe cases may be life-threatening during infancy. The milder later-onset form of glutaricaciduria II (GA IIB) may appear at any age from a few weeks to adulthood, and is associated with high levels of glutaric acid in blood and body tissues (metabolic acidosis). Low blood glucose (hypoglycemia) without accumulation of ketone bodies in blood and body tissues (ketosis) is also associated with the later-onset form of glutaricaciduria II. Both forms of glutaricaciduria II are inherited as autosomal recessive traits. (For more information on this disorder, choose "Glutaricaciduria II" as your search term in the Rare Disease Database.)

Ornithine transcarbamylase deficiency is a rare inherited metabolic disease and is one of six inherited urea cycle disorders. It is caused by a deficiency of one of the enzymes needed to break down ammonia into urea. These deficiencies cause an abnormal accumulation of ammonia in the blood and body tissues (hyperammonemia). Ornithine transcarbamylase deficiency is characterized by hyperammonemia, lack of appetite, vomiting, drowsiness, seizures, and/or coma. The liver may be abnormally enlarged (hepatomegaly). (For more information on this disorder, choose "Ornithine Transcarbamylase" as your search term in the Rare Disease Database.")

Urea cycle enzyme deficiencies (UCE) are a group of rare inherited metabolic disorders. The six disorders of the urea cycle are citrullinemia, argininosuccinic aciduria, arginase deficiency, n-acetyl glutamate synthetase deficiency, carbamyl phosphate synthetase deficiency, and ornithine transcarbamylase deficiency. The symptoms of all urea cycle disorders vary in severity and result from the excessive accumulation of ammonia in the blood and body tissues (hyperammonemia). Symptoms include lack of appetite, vomiting, drowsiness, seizures, and/or coma. The liver may be abnormally enlarged (hepatomegaly). (For more information on these disorders, choose "Citrullinemia," "Argininosuccinic Aciduria," "Arginase Deficiency," "N-Acetyl Glutamate Synthetase Deficiency," and "Caramyl Phosphate Synthetase Deficiency" as your search terms in the Rare Disease Database.)

The following disorder may be associated with short-chain Acyl-CoA dehydrogenase deficiency as a secondary characteristic. It is not necessary for a differential diagnosis:

Carnitine deficiency syndrome is a rare metabolic disorder that may be inherited or occurs as a result of other metabolic disorders. Carnitine functions in the body as a carrier of energy to the muscles. A deficiency of carnitine can cause extreme muscle weakness, vomiting, confusion, and/or coma. Carnitine deficiency syndrome may also be associated with low blood sugar and chronic heart disease. (For more information on this disorder, choose "Carnitine Deficiency" as your search term in the Rare Disease Database.)
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Diagnosis
The diagnosis of SCAD can be substantiated by a laboratory test that confirms the deficiency of the enzyme short-chain acyl-CoA dehydrogenase in connective tissue cells (fibroblasts), white blood cells (leukocytes), liver tissue, and/or muscle tissue.

As noted above, expanded newborn screening with tandem mass spectrometry is identifying more infants affected by SCAD than in the past. There is marked genetic, biochemical and clinical variation in the patients detected in the newborn screening programs. A few appear to be at risk for hypoglycemia during fasting and illnesses that involve fever, but much less so than infants with another disorder in the same group, medium chain Acyl-CoA dehydrogenase deficiency (MCAD).

Treatment
The management of patients with SCAD is modeled after treatment plans for other mitochondrial disorders. Since symptoms typically will be produced by a period of no intake of food, going a long time without eating should be avoided.

A low fat, high carbohydrate diet is recommended, with minimal periods of fasting. Sometimes children have to be awakened at night for feedings. Others may be fed intravenously or parenterally during the night. Acute episodes of acidity in the blood and dehydration are usually treated with the administration of fluids and bicarbonate. Some symptoms may be due to secondary carnitine depletion. Carnitine supplements (i.e., levocarnitine) may help to offset this deficiency.

Genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive.
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Researchers are studying heart blood flow and fatty acid metabolism using positron emission tomography (PET) scanning in individuals with inherited or acquired heart problems (cardiomyopathy). For more information, contact:

Dr. Daphne Hsu
Division of Pediatric Cardiology
(212) 305-6575

or

Dr. Steven Bergmann
Division of Pediatric Cardiology
(212) 305-7584

or

Melanie Phipps, R.N.
(212) 305-0897

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Acyl-Coa Dehydrogenase, Short-Chain; Acads. Entry Number; 606885: Last Edit Date; 7/29/2003.

TEXTBOOKS
Vockley J. Short-Chain Acyl-CoA Dehydrogenase Deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:438-39.

Metabolic Myopathies. Acyl-CoA Dehydrogenase Deficiencies. In: Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:2165-66.

Roe, CR, Ding J. Mitochondrial Fatty Acid Oxidation Disorders. In: Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:2299-300; 2315-318.

REVIEW ARTICLES
Tein I, Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy. J Child Neurol. 2002; 17 Suppl 3:3S57-82; discussion 3S82-83.

Gregersen N, Andresen BS, Corydon MJ, et al. Mutation analysis in mitochondrial Fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship. Hum Mutat. 2001;18:169-89.

Gregersen N. Andresen BS, Bross P. Prevalent mutations in fatty acid oxidation disorders: diagnostic considerations. Eur J Pediatr. 2000;159 Suppl 3:S213-18.

Gregersen N, Bross P, Jorgensen MM, et al. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders. J Inherit Metab Dis. 2000;23:441-47.

Rinaldo P. Mitochondrial fatty acid oxidation disorders and cyclic vomiting syndrome. Dig Dis Sci. 1999;44(8 Suppl):97S-102S.

JOURNAL ARTICLES
Seidel J, Streck S, Bellstedt K, et al. Recurrent vomiting and ethylmalonic aciduria associated with rare mutants of short-chain acyl-CoA dehydrogenase gene. J Inherit Metab Dis. 2003;26:37-42.

Koeberl DD, Young SP, Gregersen NS, et al. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003;54:219-23.

Van Hove JL, Grunewald S, Jaeken J, et al. D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD). Lancet. 2003;361:1433-435.

Nagan N, Kruckeberg KE, Tauscher AL, et al. The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C(4)-acylcarnitine concentration in newborn blood spots. Mol Genet Metab. 2003;78:239-46

Leonard JV, Dezateux C. Screening for inherited metabolic disease in newborn infants using tandem mass spectrometry. BMJ. 2002;324:4-5.

Marsden D, Nyhan WL, Barshop BA. Creatine kinase and uric acid: early warning for metabolic imbalance resulting from disorders of fatty acid oxidation. Eur J Pediatr. 2001;160:599-602.

Corydon MJ, Vockley J, Rinaldo P, et al. Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr Res. 2001;49:18-23.

FROM THE INTERNET
Short Chain Acyl-CoA Dehydrogenase Deficiency (SCADD). The Children’s Hospital of Boston. Last Updated: Thursday, July 24, 2003. 4pp.
http://web1.tch.Harvard.edu/newenglandconsortium/NBS/SCADD.htm

Short Chain Acyl-CoA Dehydrogenase Deficiency (SCAD). Save Babies. Last Updated: 07/10/03. 2pp.
www.savebabies.org/diseasedescriptions/scad.htm

FODs Defined. All In This Together. FOD Support Organization. nd. 10pp.
www.fodsupport.org/fods_defined.htm

Chase DH. Tandem Mass Spectrometry and Newborn Screening. A layperson’s guide. Save Babies. Revised: 5/29/03. 5pp.
www.savebabies.org/NBS/msms-chace.htm

Short chain acyl-CoA dehydrogenase deficiency. nd. 1p.
www.newbornscreening.info/FELSI/health_care/print.php?pg=h_faq_type25