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A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease
OBJECTIVES: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were r...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875587/ https://www.ncbi.nlm.nih.gov/pubmed/36712458 http://dx.doi.org/10.3389/fneur.2022.1063733 |
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author | Astner-Rohracher, Alexandra Mauritz, Matthias Leitinger, Markus Rossini, Fabio Kalss, Gudrun Neuray, Caroline Retter, Elisabeth Wortmann, Saskia B. Achleitner, Melanie T. Mayr, Johannes A. Trinka, Eugen |
author_facet | Astner-Rohracher, Alexandra Mauritz, Matthias Leitinger, Markus Rossini, Fabio Kalss, Gudrun Neuray, Caroline Retter, Elisabeth Wortmann, Saskia B. Achleitner, Melanie T. Mayr, Johannes A. Trinka, Eugen |
author_sort | Astner-Rohracher, Alexandra |
collection | PubMed |
description | OBJECTIVES: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy. CASE DESCRIPTION: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable. CONCLUSION: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations. |
format | Online Article Text |
id | pubmed-9875587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98755872023-01-26 A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease Astner-Rohracher, Alexandra Mauritz, Matthias Leitinger, Markus Rossini, Fabio Kalss, Gudrun Neuray, Caroline Retter, Elisabeth Wortmann, Saskia B. Achleitner, Melanie T. Mayr, Johannes A. Trinka, Eugen Front Neurol Neurology OBJECTIVES: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy. CASE DESCRIPTION: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable. CONCLUSION: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations. Frontiers Media S.A. 2023-01-11 /pmc/articles/PMC9875587/ /pubmed/36712458 http://dx.doi.org/10.3389/fneur.2022.1063733 Text en Copyright © 2023 Astner-Rohracher, Mauritz, Leitinger, Rossini, Kalss, Neuray, Retter, Wortmann, Achleitner, Mayr and Trinka. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Astner-Rohracher, Alexandra Mauritz, Matthias Leitinger, Markus Rossini, Fabio Kalss, Gudrun Neuray, Caroline Retter, Elisabeth Wortmann, Saskia B. Achleitner, Melanie T. Mayr, Johannes A. Trinka, Eugen A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title | A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title_full | A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title_fullStr | A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title_full_unstemmed | A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title_short | A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease |
title_sort | case report: new-onset refractory status epilepticus in a patient with fastkd2-related mitochondrial disease |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875587/ https://www.ncbi.nlm.nih.gov/pubmed/36712458 http://dx.doi.org/10.3389/fneur.2022.1063733 |
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