학술논문
Clinical variability and outcome of succinyl‐CoA:3‐ketoacid CoA transferase deficiency caused by a single OXCT1 mutation: Report of 17 cases
Document Type
Report
Source
JIMD Reports. November 2021, Vol. 62 Issue 1, p91, 6 p.
Subject
Language
English
Abstract
Synopsis Succinyl‐CoA:3‐ketoacid CoA transferase (SCOT) deficiency caused by homozygous p.R468C may have incomplete penetrance. Chronic dietary restriction and carnitine may not be warranted beyond childhood. INTRODUCTION Succinyl‐CoA:3‐oxoacid CoA transferase (SCOT) [...]
: 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.
: 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.