SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness.
Contains fulltext : 53236.pdf (Publisher’s version ) (Closed access) One pedigree with four patients has been recently described with mitochondrial DNA depletion and mutation in SUCLA2 gene leading to succinyl-CoA synthase deficiency. Patients had a Leigh-like encephalomyopathy and deafness but besi...
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Online Access: | http://hdl.handle.net/2066/53236 https://doi.org/10.1093/brain/awl389 |
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ftunivnijmegen:oai:repository.ubn.ru.nl:2066/53236 2023-11-12T04:16:58+01:00 SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Carrozzo, R. Dionisi-Vici, C. Steuerwald, U. Lucioli, S. Deodato, F. Giandomenico, S. Di Bertini, E. Franke, B. Kluijtmans, L.A.J. Meschini, M.C. Rizzo, C. Piemonte, F. Rodenburg, R.J.T. Santer, R. Santorelli, F.M. Rooij, A. van Vermunt-de Koning, D.G.M. Morava, E. Wevers, R.A. 2007 http://hdl.handle.net/2066/53236 https://doi.org/10.1093/brain/awl389 unknown http://hdl.handle.net/2066/53236 doi:10.1093/brain/awl389 Brain, 130, Pt 3, pp. 862-74 DCN 1: Perception and Action DCN 2: Functional Neurogenomics DCN 3: Neuroinformatics EBP 1: Determinants in Health and Disease IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 4: Glycostation disorders IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism NCMLS 6: Genetics and epigenetic pathways of disease UMCN 3.1: Neuromuscular development and genetic disorders UMCN 3.2: Cognitive neurosciences UMCN 5.1: Genetic defects of metabolism Article / Letter to editor 2007 ftunivnijmegen https://doi.org/10.1093/brain/awl389 2023-10-25T22:09:44Z Contains fulltext : 53236.pdf (Publisher’s version ) (Closed access) One pedigree with four patients has been recently described with mitochondrial DNA depletion and mutation in SUCLA2 gene leading to succinyl-CoA synthase deficiency. Patients had a Leigh-like encephalomyopathy and deafness but besides the presence of lactic acidosis, the profile of urine organic acid was not reported. We have studied 14 patients with mild 'unlabelled' methylmalonic aciduria (MMA) from 11 families. Eight of the families are from the Faroe Islands, having a common ancestor, and three are from southern Italy. Since the reaction catalysed by succinyl-CoA synthase in the tricarboxylic acid (TCA) cycle represents a distal step of the methylmalonic acid pathway, we investigated the SUCLA2 gene as a candidate gene in our patients. Genetic analysis of the gene in the 14 patients confirmed the defect in all patients and led to the identification of three novel mutations (p.Gly118Arg; p.Arg284Cys; c.534 + 1G --> A). The defect could be convincingly shown at the protein level and our data also confirm the previously described mitochondrial DNA depletion. Defects in SUCLA2 can be found at the metabolite level and are defined by mildly elevated methylmalonic acid and C4-dicarboxylic carnitine concentrations in body fluids in association with variable lactic acidosis. Clinically the diagnosis should be considered in patients with early/neonatal onset encephalomyopathy, dystonia, deafness and Leigh-like MRI abnormalities mainly affecting the putamen and the caudate nuclei. The frequency of the mutated allele in the Faroese population amounted to 2%, corresponding with an estimated homozygote frequency of 1 : 2500. Our data extend knowledge on the genetic defects causing MMA. Our patients present with an early infantile Leigh-like encephalomyopathy with deafness, and later on a progressive dystonia. Mild MMA, lactic acidosis and specific abnormalities in the carnitine ester profile are the biochemical hallmarks of the disease. In view of ... Article in Journal/Newspaper Faroe Islands Radboud University: DSpace Faroe Islands Brain 130 3 862 874 |
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Radboud University: DSpace |
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ftunivnijmegen |
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unknown |
topic |
DCN 1: Perception and Action DCN 2: Functional Neurogenomics DCN 3: Neuroinformatics EBP 1: Determinants in Health and Disease IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 4: Glycostation disorders IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism NCMLS 6: Genetics and epigenetic pathways of disease UMCN 3.1: Neuromuscular development and genetic disorders UMCN 3.2: Cognitive neurosciences UMCN 5.1: Genetic defects of metabolism |
spellingShingle |
DCN 1: Perception and Action DCN 2: Functional Neurogenomics DCN 3: Neuroinformatics EBP 1: Determinants in Health and Disease IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 4: Glycostation disorders IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism NCMLS 6: Genetics and epigenetic pathways of disease UMCN 3.1: Neuromuscular development and genetic disorders UMCN 3.2: Cognitive neurosciences UMCN 5.1: Genetic defects of metabolism Carrozzo, R. Dionisi-Vici, C. Steuerwald, U. Lucioli, S. Deodato, F. Giandomenico, S. Di Bertini, E. Franke, B. Kluijtmans, L.A.J. Meschini, M.C. Rizzo, C. Piemonte, F. Rodenburg, R.J.T. Santer, R. Santorelli, F.M. Rooij, A. van Vermunt-de Koning, D.G.M. Morava, E. Wevers, R.A. SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
topic_facet |
DCN 1: Perception and Action DCN 2: Functional Neurogenomics DCN 3: Neuroinformatics EBP 1: Determinants in Health and Disease IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 4: Glycostation disorders IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism NCMLS 6: Genetics and epigenetic pathways of disease UMCN 3.1: Neuromuscular development and genetic disorders UMCN 3.2: Cognitive neurosciences UMCN 5.1: Genetic defects of metabolism |
description |
Contains fulltext : 53236.pdf (Publisher’s version ) (Closed access) One pedigree with four patients has been recently described with mitochondrial DNA depletion and mutation in SUCLA2 gene leading to succinyl-CoA synthase deficiency. Patients had a Leigh-like encephalomyopathy and deafness but besides the presence of lactic acidosis, the profile of urine organic acid was not reported. We have studied 14 patients with mild 'unlabelled' methylmalonic aciduria (MMA) from 11 families. Eight of the families are from the Faroe Islands, having a common ancestor, and three are from southern Italy. Since the reaction catalysed by succinyl-CoA synthase in the tricarboxylic acid (TCA) cycle represents a distal step of the methylmalonic acid pathway, we investigated the SUCLA2 gene as a candidate gene in our patients. Genetic analysis of the gene in the 14 patients confirmed the defect in all patients and led to the identification of three novel mutations (p.Gly118Arg; p.Arg284Cys; c.534 + 1G --> A). The defect could be convincingly shown at the protein level and our data also confirm the previously described mitochondrial DNA depletion. Defects in SUCLA2 can be found at the metabolite level and are defined by mildly elevated methylmalonic acid and C4-dicarboxylic carnitine concentrations in body fluids in association with variable lactic acidosis. Clinically the diagnosis should be considered in patients with early/neonatal onset encephalomyopathy, dystonia, deafness and Leigh-like MRI abnormalities mainly affecting the putamen and the caudate nuclei. The frequency of the mutated allele in the Faroese population amounted to 2%, corresponding with an estimated homozygote frequency of 1 : 2500. Our data extend knowledge on the genetic defects causing MMA. Our patients present with an early infantile Leigh-like encephalomyopathy with deafness, and later on a progressive dystonia. Mild MMA, lactic acidosis and specific abnormalities in the carnitine ester profile are the biochemical hallmarks of the disease. In view of ... |
format |
Article in Journal/Newspaper |
author |
Carrozzo, R. Dionisi-Vici, C. Steuerwald, U. Lucioli, S. Deodato, F. Giandomenico, S. Di Bertini, E. Franke, B. Kluijtmans, L.A.J. Meschini, M.C. Rizzo, C. Piemonte, F. Rodenburg, R.J.T. Santer, R. Santorelli, F.M. Rooij, A. van Vermunt-de Koning, D.G.M. Morava, E. Wevers, R.A. |
author_facet |
Carrozzo, R. Dionisi-Vici, C. Steuerwald, U. Lucioli, S. Deodato, F. Giandomenico, S. Di Bertini, E. Franke, B. Kluijtmans, L.A.J. Meschini, M.C. Rizzo, C. Piemonte, F. Rodenburg, R.J.T. Santer, R. Santorelli, F.M. Rooij, A. van Vermunt-de Koning, D.G.M. Morava, E. Wevers, R.A. |
author_sort |
Carrozzo, R. |
title |
SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
title_short |
SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
title_full |
SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
title_fullStr |
SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
title_full_unstemmed |
SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. |
title_sort |
sucla2 mutations are associated with mild methylmalonic aciduria, leigh-like encephalomyopathy, dystonia and deafness. |
publishDate |
2007 |
url |
http://hdl.handle.net/2066/53236 https://doi.org/10.1093/brain/awl389 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_source |
Brain, 130, Pt 3, pp. 862-74 |
op_relation |
http://hdl.handle.net/2066/53236 doi:10.1093/brain/awl389 |
op_doi |
https://doi.org/10.1093/brain/awl389 |
container_title |
Brain |
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130 |
container_issue |
3 |
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862 |
op_container_end_page |
874 |
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