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New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?

OBJECTIVE: The gene MT-TF encodes the mitochondrial tRNA of phenylalanine (tRNA(phe)). Its variations have been described as extremely rare etiologies of a variety of mitochondrial phenotypes. METHODS: By means of whole-exome sequencing (WES), we detected a novel likely causative MT-TF variant (m.61...

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Autores principales: Indelicato, Elisabetta, Pfeilstetter, Johannes, Zech, Michael, Unterberger, Iris, Wanschitz, Julia, Berweck, Steffen, Boesch, Sylvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117698/
https://www.ncbi.nlm.nih.gov/pubmed/37090940
http://dx.doi.org/10.1212/NXG.0000000000200063
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author Indelicato, Elisabetta
Pfeilstetter, Johannes
Zech, Michael
Unterberger, Iris
Wanschitz, Julia
Berweck, Steffen
Boesch, Sylvia
author_facet Indelicato, Elisabetta
Pfeilstetter, Johannes
Zech, Michael
Unterberger, Iris
Wanschitz, Julia
Berweck, Steffen
Boesch, Sylvia
author_sort Indelicato, Elisabetta
collection PubMed
description OBJECTIVE: The gene MT-TF encodes the mitochondrial tRNA of phenylalanine (tRNA(phe)). Its variations have been described as extremely rare etiologies of a variety of mitochondrial phenotypes. METHODS: By means of whole-exome sequencing (WES), we detected a novel likely causative MT-TF variant (m.610T>C) in a family presenting with a combined movement disorder and epilepsy phenotype. The variant was present at 97% heteroplasmy in the peripheral blood and in a homoplasmic state in skin fibroblast-derived DNA. RESULTS: The inaugural manifestation in the index patient was new-onset refractory myoclonic status epilepticus (NORSE) at the age of 29 years. Her son presented later with developmental regression and myoclonic epilepsy. On the beginning of valproate because of ongoing myoclonic seizures, the index patient developed a generalized brain edema requiring bilateral craniotomy. In the course of the disease, epileptic manifestations abated, and both patients developed a severe movement disorder phenotype with prominent spastic-dystonic features. Both patients did not display any further sign of mitochondrial disease. DISCUSSION: Our report expands the clinicogenetic background of tRNA(phe) disease spectrum and highlights pitfalls in the diagnostics and management of mitochondrial epilepsy. The present findings advocate the introduction of rapid genetic testing in the diagnostic flow chart of NORSE in adults.
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spelling pubmed-101176982023-04-21 New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment? Indelicato, Elisabetta Pfeilstetter, Johannes Zech, Michael Unterberger, Iris Wanschitz, Julia Berweck, Steffen Boesch, Sylvia Neurol Genet Clinical/Scientific Note OBJECTIVE: The gene MT-TF encodes the mitochondrial tRNA of phenylalanine (tRNA(phe)). Its variations have been described as extremely rare etiologies of a variety of mitochondrial phenotypes. METHODS: By means of whole-exome sequencing (WES), we detected a novel likely causative MT-TF variant (m.610T>C) in a family presenting with a combined movement disorder and epilepsy phenotype. The variant was present at 97% heteroplasmy in the peripheral blood and in a homoplasmic state in skin fibroblast-derived DNA. RESULTS: The inaugural manifestation in the index patient was new-onset refractory myoclonic status epilepticus (NORSE) at the age of 29 years. Her son presented later with developmental regression and myoclonic epilepsy. On the beginning of valproate because of ongoing myoclonic seizures, the index patient developed a generalized brain edema requiring bilateral craniotomy. In the course of the disease, epileptic manifestations abated, and both patients developed a severe movement disorder phenotype with prominent spastic-dystonic features. Both patients did not display any further sign of mitochondrial disease. DISCUSSION: Our report expands the clinicogenetic background of tRNA(phe) disease spectrum and highlights pitfalls in the diagnostics and management of mitochondrial epilepsy. The present findings advocate the introduction of rapid genetic testing in the diagnostic flow chart of NORSE in adults. Wolters Kluwer 2023-03-15 /pmc/articles/PMC10117698/ /pubmed/37090940 http://dx.doi.org/10.1212/NXG.0000000000200063 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical/Scientific Note
Indelicato, Elisabetta
Pfeilstetter, Johannes
Zech, Michael
Unterberger, Iris
Wanschitz, Julia
Berweck, Steffen
Boesch, Sylvia
New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title_full New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title_fullStr New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title_full_unstemmed New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title_short New-Onset Refractory Status Epilepticus Due to a Novel MT-TF Variant: Time for Acute Genetic Testing Before Treatment?
title_sort new-onset refractory status epilepticus due to a novel mt-tf variant: time for acute genetic testing before treatment?
topic Clinical/Scientific Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117698/
https://www.ncbi.nlm.nih.gov/pubmed/37090940
http://dx.doi.org/10.1212/NXG.0000000000200063
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