Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases

Abstract Succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency is an inherited metabolic disease caused by mutated OXCT1 gene resulting in recurrent ketoacidosis. Analysis of longitudinal data in such an ultra‐rare disease is warranted to delineate genotype–phenotype correlations and management...

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Autores principales:	Malak A. Alghamdi, Mohammed Tohary, Hamad Alzaidan, Faiqa Imtiaz, Zuhair N. Al‐Hassnan
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	ketolysis OXCT1 succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency Diseases of the endocrine glands. Clinical endocrinology RC648-665 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/b00db11c18a04167b07288a6d48d296d
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spelling	oai:doaj.org-article:b00db11c18a04167b07288a6d48d296d2021-11-08T13:27:19ZClinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases2192-831210.1002/jmd2.12248https://doaj.org/article/b00db11c18a04167b07288a6d48d296d2021-11-01T00:00:00Zhttps://doi.org/10.1002/jmd2.12248https://doaj.org/toc/2192-8312Abstract Succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency is an inherited metabolic disease caused by mutated OXCT1 gene resulting in recurrent ketoacidosis. Analysis of longitudinal data in such an ultra‐rare disease is warranted to delineate genotype–phenotype correlations and management outcome. A retrospective analysis of 17 patients, from nine unrelated families, with SCOT deficiency who were followed up in the Medical Genetics Clinic at King Faisal Specialist Hospital and Research Centre was conducted. All the patients were homozygous for p.R468C in OXCT1 gene. Most of the patients (n = 15, 88.2%) were symptomatic presenting with recurrent ketoacidosis, the onset of which ranged from 6 months to 4 years (median 2 years). A striking inter‐ and intrafamilial variability that ranged from being entirely asymptomatic to death during the first episode. All patients were instructed to avoid fasting, restrict protein in diet, and receive carnitine supplementation. However, there was no correlation between following instructions of chronic management and outcome. Most of the patients had their crises resolved and all of them had normal neurodevelopmental outcome. Our data suggest that SCOT deficiency caused by homozygous p.R468C has variable clinical presentation and incomplete penetrance. The apparent lack of correlation between protein restriction +/− carnitine supplementation and outcome suggests that chronic dietary restriction may not be warranted. However, a longer follow‐up on larger and heterogenous cohort of cases is needed before a clear conclusion on the long‐term management can be reached.Malak A. AlghamdiMohammed ToharyHamad AlzaidanFaiqa ImtiazZuhair N. Al‐HassnanWileyarticleketolysisOXCT1succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiencyDiseases of the endocrine glands. Clinical endocrinologyRC648-665GeneticsQH426-470ENJIMD Reports, Vol 62, Iss 1, Pp 91-96 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ketolysis OXCT1 succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency Diseases of the endocrine glands. Clinical endocrinology RC648-665 Genetics QH426-470
spellingShingle	ketolysis OXCT1 succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency Diseases of the endocrine glands. Clinical endocrinology RC648-665 Genetics QH426-470 Malak A. Alghamdi Mohammed Tohary Hamad Alzaidan Faiqa Imtiaz Zuhair N. Al‐Hassnan Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
description	Abstract Succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency is an inherited metabolic disease caused by mutated OXCT1 gene resulting in recurrent ketoacidosis. Analysis of longitudinal data in such an ultra‐rare disease is warranted to delineate genotype–phenotype correlations and management outcome. A retrospective analysis of 17 patients, from nine unrelated families, with SCOT deficiency who were followed up in the Medical Genetics Clinic at King Faisal Specialist Hospital and Research Centre was conducted. All the patients were homozygous for p.R468C in OXCT1 gene. Most of the patients (n = 15, 88.2%) were symptomatic presenting with recurrent ketoacidosis, the onset of which ranged from 6 months to 4 years (median 2 years). A striking inter‐ and intrafamilial variability that ranged from being entirely asymptomatic to death during the first episode. All patients were instructed to avoid fasting, restrict protein in diet, and receive carnitine supplementation. However, there was no correlation between following instructions of chronic management and outcome. Most of the patients had their crises resolved and all of them had normal neurodevelopmental outcome. Our data suggest that SCOT deficiency caused by homozygous p.R468C has variable clinical presentation and incomplete penetrance. The apparent lack of correlation between protein restriction +/− carnitine supplementation and outcome suggests that chronic dietary restriction may not be warranted. However, a longer follow‐up on larger and heterogenous cohort of cases is needed before a clear conclusion on the long‐term management can be reached.
format	article
author	Malak A. Alghamdi Mohammed Tohary Hamad Alzaidan Faiqa Imtiaz Zuhair N. Al‐Hassnan
author_facet	Malak A. Alghamdi Mohammed Tohary Hamad Alzaidan Faiqa Imtiaz Zuhair N. Al‐Hassnan
author_sort	Malak A. Alghamdi
title	Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
title_short	Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
title_full	Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
title_fullStr	Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
title_full_unstemmed	Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
title_sort	clinical variability and outcome of succinyl‐coa:3‐ketoacid coa transferase deficiency caused by a single oxct1 mutation: report of 17 cases
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b00db11c18a04167b07288a6d48d296d
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Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases

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