Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series

Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical p...

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Autores principales:	Zhenchu Tang, Shan Gao, Miao He, Qihua Chen, Jia Fang, Yingying Luo, Weiqian Yan, Xiaoliu Shi, Hui Huang, Jianguang Tang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ETFDH riboflavin mutation late-onset MADD molecular analysis Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/e20ff4dec32548e2b21f04086708c4b2
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spelling	oai:doaj.org-article:e20ff4dec32548e2b21f04086708c4b22021-11-08T05:06:49ZClinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series1664-229510.3389/fneur.2021.747360https://doaj.org/article/e20ff4dec32548e2b21f04086708c4b22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.747360/fullhttps://doaj.org/toc/1664-2295Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients.Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data.Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis.Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.Zhenchu TangZhenchu TangShan GaoMiao HeMiao HeQihua ChenJia FangYingying LuoWeiqian YanXiaoliu ShiHui HuangJianguang TangFrontiers Media S.A.articleETFDHriboflavinmutationlate-onset MADDmolecular analysisNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ETFDH riboflavin mutation late-onset MADD molecular analysis Neurology. Diseases of the nervous system RC346-429
spellingShingle	ETFDH riboflavin mutation late-onset MADD molecular analysis Neurology. Diseases of the nervous system RC346-429 Zhenchu Tang Zhenchu Tang Shan Gao Miao He Miao He Qihua Chen Jia Fang Yingying Luo Weiqian Yan Xiaoliu Shi Hui Huang Jianguang Tang Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
description	Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients.Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data.Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis.Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.
format	article
author	Zhenchu Tang Zhenchu Tang Shan Gao Miao He Miao He Qihua Chen Jia Fang Yingying Luo Weiqian Yan Xiaoliu Shi Hui Huang Jianguang Tang
author_facet	Zhenchu Tang Zhenchu Tang Shan Gao Miao He Miao He Qihua Chen Jia Fang Yingying Luo Weiqian Yan Xiaoliu Shi Hui Huang Jianguang Tang
author_sort	Zhenchu Tang
title	Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
title_short	Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
title_full	Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
title_fullStr	Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
title_full_unstemmed	Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series
title_sort	clinical presentations and genetic characteristics of late-onset madd due to etfdh mutations in five patients: a case series
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e20ff4dec32548e2b21f04086708c4b2
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Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series

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