Abstract：This article reports the results of tandem mass spectrometry and the mutation features of the ETFDH gene for an infant with multiple acyl-CoA dehydrogenase defciency. The results of tandem mass spectrometry showed that C14:1, C8, C6, C10, and C12 increased. Exon sequencing was performed on this infant and his parents and revealed double heterozygous mutations in the ETFDH gene of the infant:c.992A > T and c.1450T > C. The former was inherited from his mother, and the latter was inherited from his father. c.1450T > C was shown to be the pathogenic mutation in the HGMD database. PolyPhen2, SIFT, and PROVEAN all predicted that the novel mutation c.992A > T might be pathogenic, and the mutant amino acids were highly conserved across various species. The fndings expand the mutation spectrum of the ETFDH gene, and provide molecular evidence for the etiological diagnosis of the patient with multiple acyl-CoA dehydrogenase defciency as well as for the genetic counseling and prenatal diagnosis in the family.
GAO Ang,QIAO Long-Wei,DUAN Cheng-Ying et al. A novel mutation in the ETFDH gene of an infant with multiple acyl-CoA dehydrogenase defciency[J]. CJCP, 2018, 20(7): 529-533.
Er TK, Liang WC, Chang JG, et al. High resolution melting analysis facilitates mutation screening of ETFDH gene:applications in riboflavin-responsive multiple acyl-CoA dehydrogenase defciency[J]. Clin Chim Acta, 2010, 411(9-10):690-699.
[2]
van der Westhuizen FH, Smuts I, Honey E, et al. A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency[J]. J Neurol Sci, 2018, 384:121-125.
Leone P, Galluccio M, Barbiroli A, et al. Bacterial production, characterization and protein modeling of a novel monofuctional isoform of FAD synthase in humans:an emergency protein?[J]. Molecules, 2018, 23(1):116.
[5]
Olsen RK, Broner S, Sabaratnam R, et al. The ETFDH c.158A>G variation disrupts the balanced interplay of ESE-and ESSbinding proteins thereby causing missplicing and multiple AcylCoA dehydrogenation deficiency[J]. Hum Mutat, 2014, 35(1):86-95.
[6]
Swanson MA, Usselman RJ, Frerman FE, et al. The ironsulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein[J]. Biochemistry, 2008, 47(34):8894-8901.
[7]
Grunert SC. Clinical and genetical heterogeneity of lateonset multiple acyl-coenzyme A dehydrogenase deficiency[J]. Orphanet J Rare Dis, 2014, 9:117.
[8]
Zhao YW, Liu XJ, Zhang W, et al. Muscle magnetic resonance imaging for the differentiation of multiple Acyl-CoA dehydrogenase deficiency and immune-mediated necrotizing myopathy[J]. Chin Med J (Engl), 2018, 131(2):144-150.
[9]
Wen B, Li D, Li W, et al. Multiple acyl-CoA dehydrogenation deficiency as decreased acyl-carnitine profile in serum[J]. Neurol Sci, 2015, 36(6):853-859.
[10]
Tamaoki Y, Kimura M, Hasegawa Y, et al. A survey of Japanese patients with mitochondrial fatty acid beta-oxidation and related disorders as detected from 1985 to 2000[J]. Brain Dev, 2002, 24(7):675-680.
[11]
Vengalil S, Preethish-Kumar V, Polavarapu K, et al. Fatty acid oxidation defects presenting as primary myopathy and prominent dropped head syndrome[J]. Neuromuscul Disord, 2017, 27(11):986-996.
[12]
Trebatická J, Hradečná Z, Böhmer F, et al. Emulsifed omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents:a pilot study[J]. Child Adolesc Psychiatry Ment Health, 2017, 11:30.
