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

Toshiyuki Fukao, Tomohiro Ishii, Naoko Amano, Petri Kursula, Masaki Takayanagi, Keiko Murase, Naomi Sakaguchi, Naomi Kondo, Tomonobu Hasegawa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. Here, we report a Japanese case of neonatal-onset SCOT deficiency. The male patient presented a severe ketoacidotic crisis, with blood pH of 7.072 and bicarbonate of 5.8 mmol/L at the age of 2 days and was successfully treated with intravenous infusion of glucose and sodium bicarbonate. He was diagnosed as SCOT deficient by enzymatic assay and mutation analysis. At the age of 7 months, he developed a second ketoacidotic crisis, with blood pH of 7.059, bicarbonate of 5.4 mmol/L, and total ketone bodies of 29.1 mmol/L. He experienced two milder ketoacidotic crises at the ages of 1 year and 7 months and 3 years and 7 months. His urinary ketone bodies usually range from negative to 1+ but sometimes show 3+ (ketostix) without any symptoms. Hence, this patient does not show permanent ketonuria, which is characteristic of typical SCOT-deficient patients. He is a compound heterozygote of c.1304C > A (T435N) and c.658-666dupAACGTGATT p.N220-I222dup. mutations in the OXCT1 gene. The T435N mutation was previously reported as one which retained significant residual activity. The latter novel mutation was revealed to retain no residual activity by transient expression analysis. Both T435N and N220-I222 lie close to the SCOT dimerization interface and are not directly connected to the active site in the tertiary structure of a human SCOT dimer. In transient expression analysis, no apparent interallelic complementation or dominant negative effects were observed. Significant residual activity from the T435N mutant allele may prevent the patient from developing permanent ketonuria.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
Volume33
Issue numberSUPPL. 3
DOIs
Publication statusPublished - 2010

Fingerprint

3-ketoacid CoA-transferase
Mutation
Genes
Ketone Bodies
Ketosis
Bicarbonates
Sodium Bicarbonate
Enzyme Assays
Dimerization
Nitroprusside
Heterozygote
Intravenous Infusions
succinyl-coenzyme A
Catalytic Domain
Alleles
Glucose

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

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. / Fukao, Toshiyuki; Ishii, Tomohiro; Amano, Naoko; Kursula, Petri; Takayanagi, Masaki; Murase, Keiko; Sakaguchi, Naomi; Kondo, Naomi; Hasegawa, Tomonobu.

In: Journal of Inherited Metabolic Disease, Vol. 33, No. SUPPL. 3, 2010.

Research output: Contribution to journalArticle

Fukao, Toshiyuki ; Ishii, Tomohiro ; Amano, Naoko ; Kursula, Petri ; Takayanagi, Masaki ; Murase, Keiko ; Sakaguchi, Naomi ; Kondo, Naomi ; Hasegawa, Tomonobu. / 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. In: Journal of Inherited Metabolic Disease. 2010 ; Vol. 33, No. SUPPL. 3.
@article{e41b046f1eff4637a2fdc558ff107eba,
title = "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",
abstract = "Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. Here, we report a Japanese case of neonatal-onset SCOT deficiency. The male patient presented a severe ketoacidotic crisis, with blood pH of 7.072 and bicarbonate of 5.8 mmol/L at the age of 2 days and was successfully treated with intravenous infusion of glucose and sodium bicarbonate. He was diagnosed as SCOT deficient by enzymatic assay and mutation analysis. At the age of 7 months, he developed a second ketoacidotic crisis, with blood pH of 7.059, bicarbonate of 5.4 mmol/L, and total ketone bodies of 29.1 mmol/L. He experienced two milder ketoacidotic crises at the ages of 1 year and 7 months and 3 years and 7 months. His urinary ketone bodies usually range from negative to 1+ but sometimes show 3+ (ketostix) without any symptoms. Hence, this patient does not show permanent ketonuria, which is characteristic of typical SCOT-deficient patients. He is a compound heterozygote of c.1304C > A (T435N) and c.658-666dupAACGTGATT p.N220-I222dup. mutations in the OXCT1 gene. The T435N mutation was previously reported as one which retained significant residual activity. The latter novel mutation was revealed to retain no residual activity by transient expression analysis. Both T435N and N220-I222 lie close to the SCOT dimerization interface and are not directly connected to the active site in the tertiary structure of a human SCOT dimer. In transient expression analysis, no apparent interallelic complementation or dominant negative effects were observed. Significant residual activity from the T435N mutant allele may prevent the patient from developing permanent ketonuria.",
author = "Toshiyuki Fukao and Tomohiro Ishii and Naoko Amano and Petri Kursula and Masaki Takayanagi and Keiko Murase and Naomi Sakaguchi and Naomi Kondo and Tomonobu Hasegawa",
year = "2010",
doi = "10.1007/s10545-010-9168-5",
language = "English",
volume = "33",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "SUPPL. 3",

}

TY - JOUR

T1 - A neonatal-onset succinyl-CoA

T2 - 3-ketoacid CoA transferase (SCOT)-deficient patient with T435N and c.658-666dupAACGTGATT p.N220-I222dup mutations in the OXCT1 gene

AU - Fukao, Toshiyuki

AU - Ishii, Tomohiro

AU - Amano, Naoko

AU - Kursula, Petri

AU - Takayanagi, Masaki

AU - Murase, Keiko

AU - Sakaguchi, Naomi

AU - Kondo, Naomi

AU - Hasegawa, Tomonobu

PY - 2010

Y1 - 2010

N2 - Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. Here, we report a Japanese case of neonatal-onset SCOT deficiency. The male patient presented a severe ketoacidotic crisis, with blood pH of 7.072 and bicarbonate of 5.8 mmol/L at the age of 2 days and was successfully treated with intravenous infusion of glucose and sodium bicarbonate. He was diagnosed as SCOT deficient by enzymatic assay and mutation analysis. At the age of 7 months, he developed a second ketoacidotic crisis, with blood pH of 7.059, bicarbonate of 5.4 mmol/L, and total ketone bodies of 29.1 mmol/L. He experienced two milder ketoacidotic crises at the ages of 1 year and 7 months and 3 years and 7 months. His urinary ketone bodies usually range from negative to 1+ but sometimes show 3+ (ketostix) without any symptoms. Hence, this patient does not show permanent ketonuria, which is characteristic of typical SCOT-deficient patients. He is a compound heterozygote of c.1304C > A (T435N) and c.658-666dupAACGTGATT p.N220-I222dup. mutations in the OXCT1 gene. The T435N mutation was previously reported as one which retained significant residual activity. The latter novel mutation was revealed to retain no residual activity by transient expression analysis. Both T435N and N220-I222 lie close to the SCOT dimerization interface and are not directly connected to the active site in the tertiary structure of a human SCOT dimer. In transient expression analysis, no apparent interallelic complementation or dominant negative effects were observed. Significant residual activity from the T435N mutant allele may prevent the patient from developing permanent ketonuria.

AB - Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. Here, we report a Japanese case of neonatal-onset SCOT deficiency. The male patient presented a severe ketoacidotic crisis, with blood pH of 7.072 and bicarbonate of 5.8 mmol/L at the age of 2 days and was successfully treated with intravenous infusion of glucose and sodium bicarbonate. He was diagnosed as SCOT deficient by enzymatic assay and mutation analysis. At the age of 7 months, he developed a second ketoacidotic crisis, with blood pH of 7.059, bicarbonate of 5.4 mmol/L, and total ketone bodies of 29.1 mmol/L. He experienced two milder ketoacidotic crises at the ages of 1 year and 7 months and 3 years and 7 months. His urinary ketone bodies usually range from negative to 1+ but sometimes show 3+ (ketostix) without any symptoms. Hence, this patient does not show permanent ketonuria, which is characteristic of typical SCOT-deficient patients. He is a compound heterozygote of c.1304C > A (T435N) and c.658-666dupAACGTGATT p.N220-I222dup. mutations in the OXCT1 gene. The T435N mutation was previously reported as one which retained significant residual activity. The latter novel mutation was revealed to retain no residual activity by transient expression analysis. Both T435N and N220-I222 lie close to the SCOT dimerization interface and are not directly connected to the active site in the tertiary structure of a human SCOT dimer. In transient expression analysis, no apparent interallelic complementation or dominant negative effects were observed. Significant residual activity from the T435N mutant allele may prevent the patient from developing permanent ketonuria.

UR - http://www.scopus.com/inward/record.url?scp=84897955527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897955527&partnerID=8YFLogxK

U2 - 10.1007/s10545-010-9168-5

DO - 10.1007/s10545-010-9168-5

M3 - Article

VL - 33

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - SUPPL. 3

ER -