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Erschienen in: Journal of Inherited Metabolic Disease 6/2017

10.07.2017 | Original Article

Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can develop severe ketoacidosis

verfasst von: Hideo Sasai, Yuka Aoyama, Hiroki Otsuka, Elsayed Abdelkreem, Yasuhiro Naiki, Mitsuru Kubota, Yuji Sekine, Masatsune Itoh, Mina Nakama, Hidenori Ohnishi, Ryoji Fujiki, Osamu Ohara, Toshiyuki Fukao

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 6/2017

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Abstract

Succinyl-CoA:3-oxoacid CoA transferase (SCOT, gene symbol OXCT1) deficiency is an autosomal recessive disorder in ketone body utilization that results in severe recurrent ketoacidotic episodes in infancy, including neonatal periods. More than 30 patients with this disorder have been reported and to our knowledge, their heterozygous parents and siblings have had no apparent ketoacidotic episodes. Over 5 years (2008–2012), we investigated several patients that presented with severe ketoacidosis and identified a heterozygous OXCT1 mutation in four of these cases (Case1 p.R281C, Case2 p.T435N, Case3 p.W213*, Case4 c.493delG). To confirm their heterozygous state, we performed a multiplex ligation-dependent probe amplification analysis on the OXCT1 gene which excluded the presence of large deletions or insertions in another allele. A sequencing analysis of subcloned full-length SCOT cDNA showed that wild-type cDNA clones were present at reasonable rates to mutant cDNA clones. Over the following 2 years (2013–2014), we analyzed OXCT1 mutations in six more patients presenting with severe ketoacidosis (blood pH ≦7.25 and total ketone body ≧10 mmol/L) with non-specific urinary organic acid profiles. Of these, a heterozygous OXCT1 mutation was found in two cases (Case5 p.G391D, Case6 p.R281C). Moreover, transient expression analysis revealed R281C and T435N mutants to be temperature-sensitive. This characteristic may be important because most patients developed ketoacidosis during infections. Our data indicate that heterozygous carriers of OXCT1 mutations can develop severe ketoacidotic episodes in conjunction with ketogenic stresses.
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Metadaten
Titel
Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can develop severe ketoacidosis
verfasst von
Hideo Sasai
Yuka Aoyama
Hiroki Otsuka
Elsayed Abdelkreem
Yasuhiro Naiki
Mitsuru Kubota
Yuji Sekine
Masatsune Itoh
Mina Nakama
Hidenori Ohnishi
Ryoji Fujiki
Osamu Ohara
Toshiyuki Fukao
Publikationsdatum
10.07.2017
Verlag
Springer Netherlands
Erschienen in
Journal of Inherited Metabolic Disease / Ausgabe 6/2017
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-017-0065-z

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