Biochemie und Pathobiochemie: Acetoacetat-Succinyl-CoA-Transferase-Defizienz

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Ätiologie

Ursächlich sind autosomal-rezessive Mutationen im Gen OXCT1 (5p13.1), das für die mitochondriale Acetoacetat-Succinyl-CoA- Transferase kodiert.

Pathogenese

Das Enzym katalysiert in den extrahepatischen Organen die (Re-)Aktivierung des in der Leber gebildeten Ketonkörpers Acetoacetat zu Acetoacetyl-CoA (Übertragung des CoA von Succinyl-CoA auf Acetoacetat) zur Einschleusung in die beta-Oxidation.

Klinik

• Schwere metabolische Ketoazidose
• Hypoglykämie (neonatal)
• Koma
• Krisen werden ausgelöst durch Infektionen, Fasten, körperliche Beanspruchung

Literatur

• Shafqat N, Kavanagh KL, Sass JO, et al.. “A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency”. J. Inherit. Metab. Dis., February 2013. DOI:10.1007/s10545-013-9589-z. PMID 23420214.
• Fukao T, Sass JO, Kursula P, et al.. “Clinical and molecular characterization of five patients with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency”. Biochim. Biophys. Acta, 1812:619–24, May 2011. DOI:10.1016/j.bbadis.2011.01.015. PMID 21296660.
• Fukao T, Ishii T, Amano N, et al.. “A neonatal-onset succinyl-CoA:3-ketoacid CoA transferase (SCOT)-deficient patient with T435N and c.658-666dupAACGTGATT p.N220_I222dup mutations in the OXCT1 gene”. J. Inherit. Metab. Dis., July 2010. DOI:10.1007/s10545-010-9168-5. PMID 20652411.
• Fukao T, Kursula P, Owen EP, Kondo N. “Identification and characterization of a temperature-sensitive R268H mutation in the human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene”. Mol. Genet. Metab., 92:216–21, November 2007. DOI:10.1016/j.ymgme.2007.07.005. PMID 17706444.
• Yamada K, Fukao T, Zhang G, et al.. “Single-base substitution at the last nucleotide of exon 6 (c.671G>A), resulting in the skipping of exon 6, and exons 6 and 7 in human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene”. Mol. Genet. Metab., 90:291–7, March 2007. DOI:10.1016/j.ymgme.2006.10.010. PMID 17169596.
• Fukao T, Sakurai S, Rolland MO, et al.. “A 6-bp deletion at the splice donor site of the first intron resulted in aberrant splicing using a cryptic splice site within exon 1 in a patient with succinyl-CoA: 3-Ketoacid CoA transferase (SCOT) deficiency”. Mol. Genet. Metab., 89:280–2, November 2006. DOI:10.1016/j.ymgme.2006.04.014. PMID 16765626.
• Longo N, Fukao T, Singh R, et al.. “Succinyl-CoA:3-ketoacid transferase (SCOT) deficiency in a new patient homozygous for an R217X mutation”. J. Inherit. Metab. Dis., 27:691–2, 2004. PMID 15669687.
• Fukao T, Shintaku H, Kusubae R, et al.. “Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA Transferase (SCOT) do not show permanent ketosis”. Pediatr. Res., 56:858–63, December 2004. DOI:10.1203/01.PDR.0000145297.90577.67. PMID 15496607.
• Berry GT, Fukao T, Mitchell GA, et al.. “Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency”. J. Inherit. Metab. Dis., 24:587–95, October 2001. PMID 11757586.
• Fukao T, Mitchell GA, Song XQ, et al.. “Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations”. Genomics, 68:144–51, September 2000. DOI:10.1006/geno.2000.6282. PMID 10964512.
• Song XQ, Fukao T, Watanabe H, et al.. <83::AID-HUMU2>3.0.CO;2-P “Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic mutations, V133E and C456F, in Japanese siblings”. Hum. Mutat., 12:83–8, 1998. DOI:<83::AID-HUMU2>3.0.CO;2-P 10.1002/(SICI)1098-1004(1998)12:2<83::AID-HUMU2>3.0.CO;2-P. PMID 9671268.
• Song XQ, Fukao T, Mitchell GA, et al.. “Succinyl-CoA:3-ketoacid coenzyme A transferase (SCOT): development of an antibody to human SCOT and diagnostic use in hereditary SCOT deficiency”. Biochim. Biophys. Acta, 1360:151–6, April 1997. PMID 9128180.
• Kassovska-Bratinova S, Fukao T, Song XQ, et al.. “Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient”. Am. J. Hum. Genet., 59:519–28, September 1996. PMID 8751852.
• Fukao T, Song XQ, Watanabe H, et al.. “Prenatal diagnosis of succinyl-coenzyme A:3-ketoacid coenzyme A transferase deficiency”. Prenat. Diagn., 16:471–4, May 1996. DOI:<471::AID-PD898>3.0.CO;2-E 10.1002/(SICI)1097-0223(199605)16:5<471::AID-PD898>3.0.CO;2-E. PMID 8844009.

Weblinks

• OMIM

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