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Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations

OBJECTIVE: To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden. METHODS: Clinical assessments, targeted genetic studies, neuroimaging with MRI, [(18)F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with (123)I FP-CIT (DaTscan) SPEC...

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Autores principales: Niemelä, Valter, Salih, Ammar, Solea, Daniela, Lindvall, Björn, Weinberg, Jan, Miltenberger, Gabriel, Granberg, Tobias, Tzovla, Aikaterini, Nordin, Love, Danfors, Torsten, Savitcheva, Irina, Dahl, Niklas, Paucar, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217656/
https://www.ncbi.nlm.nih.gov/pubmed/32494755
http://dx.doi.org/10.1212/NXG.0000000000000426
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author Niemelä, Valter
Salih, Ammar
Solea, Daniela
Lindvall, Björn
Weinberg, Jan
Miltenberger, Gabriel
Granberg, Tobias
Tzovla, Aikaterini
Nordin, Love
Danfors, Torsten
Savitcheva, Irina
Dahl, Niklas
Paucar, Martin
author_facet Niemelä, Valter
Salih, Ammar
Solea, Daniela
Lindvall, Björn
Weinberg, Jan
Miltenberger, Gabriel
Granberg, Tobias
Tzovla, Aikaterini
Nordin, Love
Danfors, Torsten
Savitcheva, Irina
Dahl, Niklas
Paucar, Martin
author_sort Niemelä, Valter
collection PubMed
description OBJECTIVE: To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden. METHODS: Clinical assessments, targeted genetic studies, neuroimaging with MRI, [(18)F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with (123)I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS). RESULTS: Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea. CONCLUSIONS: Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.
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spelling pubmed-72176562020-06-02 Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations Niemelä, Valter Salih, Ammar Solea, Daniela Lindvall, Björn Weinberg, Jan Miltenberger, Gabriel Granberg, Tobias Tzovla, Aikaterini Nordin, Love Danfors, Torsten Savitcheva, Irina Dahl, Niklas Paucar, Martin Neurol Genet Article OBJECTIVE: To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden. METHODS: Clinical assessments, targeted genetic studies, neuroimaging with MRI, [(18)F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with (123)I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS). RESULTS: Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea. CONCLUSIONS: Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc. Wolters Kluwer 2020-04-27 /pmc/articles/PMC7217656/ /pubmed/32494755 http://dx.doi.org/10.1212/NXG.0000000000000426 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Niemelä, Valter
Salih, Ammar
Solea, Daniela
Lindvall, Björn
Weinberg, Jan
Miltenberger, Gabriel
Granberg, Tobias
Tzovla, Aikaterini
Nordin, Love
Danfors, Torsten
Savitcheva, Irina
Dahl, Niklas
Paucar, Martin
Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title_full Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title_fullStr Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title_full_unstemmed Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title_short Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
title_sort phenotypic variability in chorea-acanthocytosis associated with novel vps13a mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217656/
https://www.ncbi.nlm.nih.gov/pubmed/32494755
http://dx.doi.org/10.1212/NXG.0000000000000426
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