Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): Case reports and epidemiology of ETFDH gene mutations

Wei Chen, Youqiao Zhang, Yifeng Ni, Shaoyu Cai, Xin Zheng, Frank L. Mastaglia, Jingshan Wu

Research output: Contribution to journalArticle

Abstract

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a riboflavin-responsive lipid-storage myopathy caused by mutations in the EFTA, EFTB or ETFDH genes. We report a Chinese family of Southern Min origin with two affected siblings with late-onset riboflavin-responsive MADD due to a homozygous c.250G > A EFTDH mutation and review the genetic epidemiology of the c.250G > A mutation. Case presentation: Both siblings presented with exercise-induced myalgia, progressive proximal muscle weakness and high levels of serum muscle enzymes and were initially diagnosed as polymyositis after a muscle biopsy. A repeat biopsy in one sibling subsequently showed features of lipid storage myopathy and genetic analysis identified a homozygous mutation (c.250G > A) in the ETFDH gene in both siblings and carriage of the same mutation by both parents. Glucocorticoid therapy led to improvement in muscle enzyme levels, but little change in muscle symptoms, and only after treatment with riboflavin was there marked improvement in exercise tolerance and muscle strength. The frequency and geographic distribution of the c.250G > A mutation were determined from a literature search for all previously reported cases of MADD with documented mutations. Our study found the c.250G > A mutation is the most common EFTDH mutation in riboflavin-responsive MADD (RR-MADD) and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries. Conclusions: Mutations in ETFDH should be screened for in individuals with lipid-storage myopathy to identify patients who are responsive to riboflavin. The c.250G > A mutation should be suspected particularly in individuals of southern Min Chinese background.

Original languageEnglish
Article number330
JournalBMC Neurology
Volume19
Issue number1
DOIs
Publication statusPublished - 18 Dec 2019

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Multiple Acyl Coenzyme A Dehydrogenase Deficiency
Riboflavin
Epidemiology
Mutation
Genes
Siblings
Muscles
China
Biopsy
Polymyositis
Exercise Tolerance
Far East
Molecular Epidemiology
Myalgia
Muscle Weakness
Muscle Strength
Enzymes
Glucocorticoids

Cite this

@article{f707739e52fa49f9b1a06592bcb2c82e,
title = "Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): Case reports and epidemiology of ETFDH gene mutations",
abstract = "Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a riboflavin-responsive lipid-storage myopathy caused by mutations in the EFTA, EFTB or ETFDH genes. We report a Chinese family of Southern Min origin with two affected siblings with late-onset riboflavin-responsive MADD due to a homozygous c.250G > A EFTDH mutation and review the genetic epidemiology of the c.250G > A mutation. Case presentation: Both siblings presented with exercise-induced myalgia, progressive proximal muscle weakness and high levels of serum muscle enzymes and were initially diagnosed as polymyositis after a muscle biopsy. A repeat biopsy in one sibling subsequently showed features of lipid storage myopathy and genetic analysis identified a homozygous mutation (c.250G > A) in the ETFDH gene in both siblings and carriage of the same mutation by both parents. Glucocorticoid therapy led to improvement in muscle enzyme levels, but little change in muscle symptoms, and only after treatment with riboflavin was there marked improvement in exercise tolerance and muscle strength. The frequency and geographic distribution of the c.250G > A mutation were determined from a literature search for all previously reported cases of MADD with documented mutations. Our study found the c.250G > A mutation is the most common EFTDH mutation in riboflavin-responsive MADD (RR-MADD) and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries. Conclusions: Mutations in ETFDH should be screened for in individuals with lipid-storage myopathy to identify patients who are responsive to riboflavin. The c.250G > A mutation should be suspected particularly in individuals of southern Min Chinese background.",
keywords = "C.250G > A mutation, Epidemiology, ETFDH gene, Late-onset multiple acyl-CoA dehydrogenase deficiency, Lipid storage myopathy, Southern min population",
author = "Wei Chen and Youqiao Zhang and Yifeng Ni and Shaoyu Cai and Xin Zheng and Mastaglia, {Frank L.} and Jingshan Wu",
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Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) : Case reports and epidemiology of ETFDH gene mutations. / Chen, Wei; Zhang, Youqiao; Ni, Yifeng; Cai, Shaoyu; Zheng, Xin; Mastaglia, Frank L.; Wu, Jingshan.

In: BMC Neurology, Vol. 19, No. 1, 330, 18.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD)

T2 - Case reports and epidemiology of ETFDH gene mutations

AU - Chen, Wei

AU - Zhang, Youqiao

AU - Ni, Yifeng

AU - Cai, Shaoyu

AU - Zheng, Xin

AU - Mastaglia, Frank L.

AU - Wu, Jingshan

PY - 2019/12/18

Y1 - 2019/12/18

N2 - Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a riboflavin-responsive lipid-storage myopathy caused by mutations in the EFTA, EFTB or ETFDH genes. We report a Chinese family of Southern Min origin with two affected siblings with late-onset riboflavin-responsive MADD due to a homozygous c.250G > A EFTDH mutation and review the genetic epidemiology of the c.250G > A mutation. Case presentation: Both siblings presented with exercise-induced myalgia, progressive proximal muscle weakness and high levels of serum muscle enzymes and were initially diagnosed as polymyositis after a muscle biopsy. A repeat biopsy in one sibling subsequently showed features of lipid storage myopathy and genetic analysis identified a homozygous mutation (c.250G > A) in the ETFDH gene in both siblings and carriage of the same mutation by both parents. Glucocorticoid therapy led to improvement in muscle enzyme levels, but little change in muscle symptoms, and only after treatment with riboflavin was there marked improvement in exercise tolerance and muscle strength. The frequency and geographic distribution of the c.250G > A mutation were determined from a literature search for all previously reported cases of MADD with documented mutations. Our study found the c.250G > A mutation is the most common EFTDH mutation in riboflavin-responsive MADD (RR-MADD) and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries. Conclusions: Mutations in ETFDH should be screened for in individuals with lipid-storage myopathy to identify patients who are responsive to riboflavin. The c.250G > A mutation should be suspected particularly in individuals of southern Min Chinese background.

AB - Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a riboflavin-responsive lipid-storage myopathy caused by mutations in the EFTA, EFTB or ETFDH genes. We report a Chinese family of Southern Min origin with two affected siblings with late-onset riboflavin-responsive MADD due to a homozygous c.250G > A EFTDH mutation and review the genetic epidemiology of the c.250G > A mutation. Case presentation: Both siblings presented with exercise-induced myalgia, progressive proximal muscle weakness and high levels of serum muscle enzymes and were initially diagnosed as polymyositis after a muscle biopsy. A repeat biopsy in one sibling subsequently showed features of lipid storage myopathy and genetic analysis identified a homozygous mutation (c.250G > A) in the ETFDH gene in both siblings and carriage of the same mutation by both parents. Glucocorticoid therapy led to improvement in muscle enzyme levels, but little change in muscle symptoms, and only after treatment with riboflavin was there marked improvement in exercise tolerance and muscle strength. The frequency and geographic distribution of the c.250G > A mutation were determined from a literature search for all previously reported cases of MADD with documented mutations. Our study found the c.250G > A mutation is the most common EFTDH mutation in riboflavin-responsive MADD (RR-MADD) and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries. Conclusions: Mutations in ETFDH should be screened for in individuals with lipid-storage myopathy to identify patients who are responsive to riboflavin. The c.250G > A mutation should be suspected particularly in individuals of southern Min Chinese background.

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KW - Epidemiology

KW - ETFDH gene

KW - Late-onset multiple acyl-CoA dehydrogenase deficiency

KW - Lipid storage myopathy

KW - Southern min population

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DO - 10.1186/s12883-019-1562-5

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