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Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency.
Neurol Sci. 2016 Jul; 37(7):1099-105.NS

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27000805

Citation

Fu, Hong-Xia, et al. "Significant Clinical Heterogeneity With Similar ETFDH Genotype in Three Chinese Patients With Late-onset Multiple acyl-CoA Dehydrogenase Deficiency." Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, vol. 37, no. 7, 2016, pp. 1099-105.
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. 2016;37(7):1099-105.
Fu, H. X., Liu, X. Y., Wang, Z. Q., Jin, M., Wang, D. N., He, J. J., Lin, M. T., & Wang, N. (2016). Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 37(7), 1099-105. https://doi.org/10.1007/s10072-016-2549-2
Fu HX, et al. Significant Clinical Heterogeneity With Similar ETFDH Genotype in Three Chinese Patients With Late-onset Multiple acyl-CoA Dehydrogenase Deficiency. Neurol Sci. 2016;37(7):1099-105. PubMed PMID: 27000805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. AU - Fu,Hong-Xia, AU - Liu,Xin-Yi, AU - Wang,Zhi-Qiang, AU - Jin,Ming, AU - Wang,Dan-Ni, AU - He,Jun-Jie, AU - Lin,Min-Ting, AU - Wang,Ning, Y1 - 2016/03/21/ PY - 2015/10/18/received PY - 2016/03/04/accepted PY - 2016/3/23/entrez PY - 2016/3/24/pubmed PY - 2017/1/26/medline KW - Clinical heterogeneity KW - ETFDH KW - Late-onset multiple acyl-CoA dehydrogenase deficiency KW - Lipid storage myopathy KW - Variants SP - 1099 EP - 105 JF - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology JO - Neurol. Sci. VL - 37 IS - 7 N2 - 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. SN - 1590-3478 UR - https://www.unboundmedicine.com/medline/citation/27000805/Significant_clinical_heterogeneity_with_similar_ETFDH_genotype_in_three_Chinese_patients_with_late_onset_multiple_acyl_CoA_dehydrogenase_deficiency_ L2 - https://dx.doi.org/10.1007/s10072-016-2549-2 DB - PRIME DP - Unbound Medicine ER -