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Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy
A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood and was diagnosed with Charcot–Marie–Tooth disease (CMT) at age 15. She developed recurrent, fever-induced rhabdomyolysis (RM) at age 24. EMG studies showed decreased amplitude of compound muscle action potent...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546186/ https://www.ncbi.nlm.nih.gov/pubmed/34712195 http://dx.doi.org/10.3389/fneur.2021.694966 |
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author | Guan, Yuqing Zhang, Yanxia Shen, Xin-Ming Zhou, Liang Shang, Xuan Peng, Yu Hu, Yafang Li, Wei |
author_facet | Guan, Yuqing Zhang, Yanxia Shen, Xin-Ming Zhou, Liang Shang, Xuan Peng, Yu Hu, Yafang Li, Wei |
author_sort | Guan, Yuqing |
collection | PubMed |
description | A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood and was diagnosed with Charcot–Marie–Tooth disease (CMT) at age 15. She developed recurrent, fever-induced rhabdomyolysis (RM) at age 24. EMG studies showed decreased amplitude of compound muscle action potential, declined motor conductive velocity, and absence of sensor nerve action potential. Acylcarnitine analysis revealed elevated C16-OH, C18-OH, and C18:1-OH. Muscle biopsy showed scattered foci of necrotic myofibers invaded by macrophages, occasional regenerating fibers, and remarkable muscle fiber type grouping. Whole-exome sequencing identified two novel heterozygous mutations: c.490G>A (p.G164S) and c.686G>A (p.R229Q) in HADHB gene encoding the β-subunit of mitochondrial trifunctional protein (MTP). Reduction of long-chain fatty acid via dietary restrictions alleviated symptoms effectively. Our study indicates that the defect of the MTP β-subunit accounts for both CMT and RM in the same patient and expands the clinical spectrum of disorders caused by the HADHB mutations. Our systematic review of all MTPD patients with dietary treatment indicates that the effect of dietary treatment is related to the age of onset and the severity of symptoms. |
format | Online Article Text |
id | pubmed-8546186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85461862021-10-27 Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy Guan, Yuqing Zhang, Yanxia Shen, Xin-Ming Zhou, Liang Shang, Xuan Peng, Yu Hu, Yafang Li, Wei Front Neurol Neurology A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood and was diagnosed with Charcot–Marie–Tooth disease (CMT) at age 15. She developed recurrent, fever-induced rhabdomyolysis (RM) at age 24. EMG studies showed decreased amplitude of compound muscle action potential, declined motor conductive velocity, and absence of sensor nerve action potential. Acylcarnitine analysis revealed elevated C16-OH, C18-OH, and C18:1-OH. Muscle biopsy showed scattered foci of necrotic myofibers invaded by macrophages, occasional regenerating fibers, and remarkable muscle fiber type grouping. Whole-exome sequencing identified two novel heterozygous mutations: c.490G>A (p.G164S) and c.686G>A (p.R229Q) in HADHB gene encoding the β-subunit of mitochondrial trifunctional protein (MTP). Reduction of long-chain fatty acid via dietary restrictions alleviated symptoms effectively. Our study indicates that the defect of the MTP β-subunit accounts for both CMT and RM in the same patient and expands the clinical spectrum of disorders caused by the HADHB mutations. Our systematic review of all MTPD patients with dietary treatment indicates that the effect of dietary treatment is related to the age of onset and the severity of symptoms. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8546186/ /pubmed/34712195 http://dx.doi.org/10.3389/fneur.2021.694966 Text en Copyright © 2021 Guan, Zhang, Shen, Zhou, Shang, Peng, Hu and Li. 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 Guan, Yuqing Zhang, Yanxia Shen, Xin-Ming Zhou, Liang Shang, Xuan Peng, Yu Hu, Yafang Li, Wei Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title | Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title_full | Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title_fullStr | Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title_full_unstemmed | Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title_short | Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy |
title_sort | charcot–marie–tooth disease with episodic rhabdomyolysis due to two novel mutations in the β subunit of mitochondrial trifunctional protein and effective response to modified diet therapy |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546186/ https://www.ncbi.nlm.nih.gov/pubmed/34712195 http://dx.doi.org/10.3389/fneur.2021.694966 |
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