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.
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Acknowledgments
We thank the patients and their family members for their cooperation. This work was supported by Grants from the National Natural Science Foundation of China (81271254, Beijing), National Key Clinical Specialty Discipline Construction Program, and Fujian Key Clinical Specialty Discipline Construction Program.
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This study was funded by Grants from the National Natural Science Foundation of China (Grant Number: 81271254), National Key Clinical Specialty Discipline Construction Program, and Fujian Key Clinical Specialty Discipline Construction Program.
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The authors declare that they have no conflict of interest.
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H. Fu and X. Liu contributed equally to this work.
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Fu, Hx., Liu, Xy., Wang, Zq. et al. Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Neurol Sci 37, 1099–1105 (2016). https://doi.org/10.1007/s10072-016-2549-2
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DOI: https://doi.org/10.1007/s10072-016-2549-2