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Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene
Methylmalonyl-coA epimerase (MCE) follows propionyl-coA carboxylase and precedes methylmalonyl-coA mutase in the pathway converting propionyl-coA to succinyl-coA. MCE deficiency has previously been described in six patients, one presenting with metabolic acidosis, the others with nonspecific neurolo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037260/ https://www.ncbi.nlm.nih.gov/pubmed/27699154 http://dx.doi.org/10.1016/j.ymgmr.2016.09.001 |
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author | Waters, Paula J. Thuriot, Fanny Clarke, Joe T.R. Gravel, Serge Watkins, David Rosenblatt, David S. Lévesque, Sébastien |
author_facet | Waters, Paula J. Thuriot, Fanny Clarke, Joe T.R. Gravel, Serge Watkins, David Rosenblatt, David S. Lévesque, Sébastien |
author_sort | Waters, Paula J. |
collection | PubMed |
description | Methylmalonyl-coA epimerase (MCE) follows propionyl-coA carboxylase and precedes methylmalonyl-coA mutase in the pathway converting propionyl-coA to succinyl-coA. MCE deficiency has previously been described in six patients, one presenting with metabolic acidosis, the others with nonspecific neurological symptoms or asymptomatic. The clinical significance and biochemical characteristics of this rare condition have been incompletely defined. We now describe a patient who presented acutely at 5 years of age with vomiting, dehydration, confusion, severe metabolic acidosis and mild hyperammonemia. At presentation, organic acid profiles were dominated by increased ketones and 3-hydroxypropionate, with moderately elevated methylcitrate and propionylglycine, and acylcarnitine profiles showed marked C3 (propionylcarnitine) elevation with normal C4DC (methylmalonylcarnitine + succinylcarnitine). Propionic acidemia was initially suspected, but it was subsequently noted that methylmalonic acid was mildly but persistently elevated in urine, and clearly elevated in plasma and cerebrospinal fluid. The overall biochemical profile prompted consideration of MCE deficiency. Studies on cultured fibroblasts showed moderately decreased propionate incorporation. Complementation analysis permitted assignment to the MCEE group. A heterozygous p.Arg47Ter (p.R47*) mutation in the MCEE gene was identified by sequencing of exons, and RNA studies identified a novel intronic splicing mutation, c.379-644A > G, confirming the diagnosis of MCE deficiency. Following the initial severe presentation, development has been normal and the clinical course over the subsequent six years has remained relatively uneventful on an essentially normal diet. This report contributes to the clinical and biochemical characterisation of this rare disorder, while highlighting potential causes of under-diagnosis or of diagnostic confusion. |
format | Online Article Text |
id | pubmed-5037260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-50372602016-10-03 Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene Waters, Paula J. Thuriot, Fanny Clarke, Joe T.R. Gravel, Serge Watkins, David Rosenblatt, David S. Lévesque, Sébastien Mol Genet Metab Rep Case Report Methylmalonyl-coA epimerase (MCE) follows propionyl-coA carboxylase and precedes methylmalonyl-coA mutase in the pathway converting propionyl-coA to succinyl-coA. MCE deficiency has previously been described in six patients, one presenting with metabolic acidosis, the others with nonspecific neurological symptoms or asymptomatic. The clinical significance and biochemical characteristics of this rare condition have been incompletely defined. We now describe a patient who presented acutely at 5 years of age with vomiting, dehydration, confusion, severe metabolic acidosis and mild hyperammonemia. At presentation, organic acid profiles were dominated by increased ketones and 3-hydroxypropionate, with moderately elevated methylcitrate and propionylglycine, and acylcarnitine profiles showed marked C3 (propionylcarnitine) elevation with normal C4DC (methylmalonylcarnitine + succinylcarnitine). Propionic acidemia was initially suspected, but it was subsequently noted that methylmalonic acid was mildly but persistently elevated in urine, and clearly elevated in plasma and cerebrospinal fluid. The overall biochemical profile prompted consideration of MCE deficiency. Studies on cultured fibroblasts showed moderately decreased propionate incorporation. Complementation analysis permitted assignment to the MCEE group. A heterozygous p.Arg47Ter (p.R47*) mutation in the MCEE gene was identified by sequencing of exons, and RNA studies identified a novel intronic splicing mutation, c.379-644A > G, confirming the diagnosis of MCE deficiency. Following the initial severe presentation, development has been normal and the clinical course over the subsequent six years has remained relatively uneventful on an essentially normal diet. This report contributes to the clinical and biochemical characterisation of this rare disorder, while highlighting potential causes of under-diagnosis or of diagnostic confusion. Elsevier 2016-09-24 /pmc/articles/PMC5037260/ /pubmed/27699154 http://dx.doi.org/10.1016/j.ymgmr.2016.09.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Case Report Waters, Paula J. Thuriot, Fanny Clarke, Joe T.R. Gravel, Serge Watkins, David Rosenblatt, David S. Lévesque, Sébastien Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title | Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title_full | Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title_fullStr | Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title_full_unstemmed | Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title_short | Methylmalonyl-coA epimerase deficiency: A new case, with an acute metabolic presentation and an intronic splicing mutation in the MCEE gene |
title_sort | methylmalonyl-coa epimerase deficiency: a new case, with an acute metabolic presentation and an intronic splicing mutation in the mcee gene |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037260/ https://www.ncbi.nlm.nih.gov/pubmed/27699154 http://dx.doi.org/10.1016/j.ymgmr.2016.09.001 |
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