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Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction...

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Autores principales: Ogawa, Erika, Shimura, Masaru, Fushimi, Takuya, Tajika, Makiko, Ichimoto, Keiko, Matsunaga, Ayako, Tsuruoka, Tomoko, Ishige, Mika, Fuchigami, Tatsuo, Yamazaki, Taro, Mori, Masato, Kohda, Masakazu, Kishita, Yoshihito, Okazaki, Yasushi, Takahashi, Shori, Ohtake, Akira, Murayama, Kei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579154/
https://www.ncbi.nlm.nih.gov/pubmed/28429146
http://dx.doi.org/10.1007/s10545-017-0042-6
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author Ogawa, Erika
Shimura, Masaru
Fushimi, Takuya
Tajika, Makiko
Ichimoto, Keiko
Matsunaga, Ayako
Tsuruoka, Tomoko
Ishige, Mika
Fuchigami, Tatsuo
Yamazaki, Taro
Mori, Masato
Kohda, Masakazu
Kishita, Yoshihito
Okazaki, Yasushi
Takahashi, Shori
Ohtake, Akira
Murayama, Kei
author_facet Ogawa, Erika
Shimura, Masaru
Fushimi, Takuya
Tajika, Makiko
Ichimoto, Keiko
Matsunaga, Ayako
Tsuruoka, Tomoko
Ishige, Mika
Fuchigami, Tatsuo
Yamazaki, Taro
Mori, Masato
Kohda, Masakazu
Kishita, Yoshihito
Okazaki, Yasushi
Takahashi, Shori
Ohtake, Akira
Murayama, Kei
author_sort Ogawa, Erika
collection PubMed
description Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10545-017-0042-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-55791542017-09-18 Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients Ogawa, Erika Shimura, Masaru Fushimi, Takuya Tajika, Makiko Ichimoto, Keiko Matsunaga, Ayako Tsuruoka, Tomoko Ishige, Mika Fuchigami, Tatsuo Yamazaki, Taro Mori, Masato Kohda, Masakazu Kishita, Yoshihito Okazaki, Yasushi Takahashi, Shori Ohtake, Akira Murayama, Kei J Inherit Metab Dis Original Article Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10545-017-0042-6) contains supplementary material, which is available to authorized users. Springer Netherlands 2017-04-20 2017 /pmc/articles/PMC5579154/ /pubmed/28429146 http://dx.doi.org/10.1007/s10545-017-0042-6 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Ogawa, Erika
Shimura, Masaru
Fushimi, Takuya
Tajika, Makiko
Ichimoto, Keiko
Matsunaga, Ayako
Tsuruoka, Tomoko
Ishige, Mika
Fuchigami, Tatsuo
Yamazaki, Taro
Mori, Masato
Kohda, Masakazu
Kishita, Yoshihito
Okazaki, Yasushi
Takahashi, Shori
Ohtake, Akira
Murayama, Kei
Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title_full Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title_fullStr Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title_full_unstemmed Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title_short Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients
title_sort clinical validity of biochemical and molecular analysis in diagnosing leigh syndrome: a study of 106 japanese patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579154/
https://www.ncbi.nlm.nih.gov/pubmed/28429146
http://dx.doi.org/10.1007/s10545-017-0042-6
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