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Neurol Sci. 2016 Jul;37(7):1099-105. doi: 10.1007/s10072-016-2549-2. Epub 2016 Mar 21.

Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency.

Author information

1
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China.
2
Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.
3
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China. ningwang@mail.fjmu.edu.cn.
4
Fujian Key Laboratory of Molecular Neurology, Fuzhou, China. ningwang@mail.fjmu.edu.cn.

Abstract

Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) with electron transfer flavoprotein dehydrogenase (ETFDH) gene mutations is the most common lipid storage myopathy (LSM) in China. Its clinical features vary widely and pose a challenge for diagnosis. We presented the significant clinical heterogeneity among three Chinese late-onset MADD patients with similar ETFDH genotype by collecting clinical information, muscle histology, and genetic analysis. Three novel compound heterozygous variants of ETFDH gene were identified: c.892C > T (p.Pro298Ser), c.453delA (p.Glu152ArgfsTer15), and c.449_453delTAACA (p.Leu150Ter). Moreover, all patients carried a hotspot mutation c.250G > A (p.Ala84Thr). Western blot analysis of the patients' muscular tissue showed a significantly reduced ETFDH expression, and normal electron transfer flavoprotein A (ETFA) and electron transfer flavoprotein B (ETFB) expression. Two patients with similar genotypes (c.453delA and c.449_453delTAACA) presented a significant clinical heterogeneity. Among them, one exhibited muscle weakness and exercise intolerance as initial and major symptoms, and the other showed episodic recurrent gastrointestinal symptoms before a serious muscle weakness appeared in later life. The novel variants in ETFDH and the corresponding clinical features enrich the variant spectrum of late-onset MADD and provide a new insight into the genotype-phenotype relationship. Late-onset MADD should be included in differential diagnosis for adult myopathy along with chronic digestive disease.

KEYWORDS:

Clinical heterogeneity; ETFDH; Late-onset multiple acyl-CoA dehydrogenase deficiency; Lipid storage myopathy; Variants

PMID:
27000805
DOI:
10.1007/s10072-016-2549-2
[Indexed for MEDLINE]

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