Short-chain acyl-coenzyme A dehydrogenase deficiency
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|Short-chain acyl-coenzyme A dehydrogenase deficiency|
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Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD), also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.
Some affected infants will exhibit vomiting, low blood sugar (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delays, and a small head size (microcephaly). The symptoms of short-chain acyl-CoA dehydrogenase deficiency may be triggered by periods of fasting or during illnesses such as viral infections. In some cases, signs and symptoms may not appear until adulthood, when some individuals may develop muscle weakness and wasting. Other people with gene mutations that can cause this disorder may have such mild symptoms that they are never diagnosed. Many biochemical geneticists consider this to be a biochemical phenotype with a very mild clinical phenotype or no clinical phenotype.
Cause and Genetics
SCADD is caused by mutations in the ACADS gene, located on chromosome 12q22-qter. Mutations in the ACADS gene lead to inadequate levels of an enzyme called short-chain acyl-CoA dehydrogenase, which is important for the breakdown of short-chain fatty acids. Reduced levels of this enzyme prevent short-chain fatty acids from being further broken down and processed in the mitochondria (the energy-producing centers inside cells). As a result, these short-chain fatty acids are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy and hypoglycemia.
The disorder is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 12 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
This disorder is thought to affect approximately 1 in 50,000 newborns.
- Online 'Mendelian Inheritance in Man' (OMIM) 201470
- Jethva R, B. M.; Bennett, M.; Vockley, J. (Dec 2008). "Mini-Review: Short-Chain Acyl-Coenzyme A Dehydrogenase Deficiency". Molecular Genetics and Metabolism (Free full text) 95 (4): 195–200. doi:10.1016/j.ymgme.2008.09.007. PMC 2720545. PMID 18977676.
- Tein I, Elpeleg O, Ben-Zeev B, et al. (Feb 2008). "Short-chain acyl-CoA dehydrogenase gene mutation (c.319C>T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin". Mol. Genet. Metab. 93 (2): 179–189. doi:10.1016/j.ymgme.2007.09.021. PMID 18054510.
- Online 'Mendelian Inheritance in Man' (OMIM) 606885
- GeneReviews/NCBI/NIH/UW entry on Short-Chain Acyl-CoA Dehydrogenase Deficiency
- Short-chain acyl-coenzyme A dehydrogenase deficiency at NLM Genetics Home Reference
- ACADS gene
- Short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) deficiency at NIH's Office of Rare Diseases
- "Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCAD)". Save Babies Through Screening Foundation.
- "Acyl CoA dehydrogenase, short chain, deficiency of". Orphanet.
- "SCAD". Disease Information from NORD, National Organization for Rare Disorders, Inc.
- Bok LA, Vreken P, Wijburg FA, et al. (November 2003). "Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding to the complexity of the disorder". Pediatrics 112 (5): 1152–5. doi:10.1542/peds.112.5.1152. PMID 14595061.