A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency

Van der Westhuizen, Francois H.Smuts, IzelleHoney, Engela M.Louw, RoanSchoonen, MarykeJonck, Lindi-MarynDercksen, Marli2018-06-182018-01Van der Westhuizen, F.H., Smuts, I., Honey, E. et al. 2018, 'A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency', Journal of the Neurological Sciences, vol. 384, pp. 121-125.0022-510X (print)1878-5883 (online)10.1016/j.jns.2017.11.012http://hdl.handle.net/2263/65165Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD type I) is an autosomal recessive disorder of the electron transfer flavoprotein function characterized by a severe clinical and biochemical phenotype, including congenital abnormalities with unresponsiveness to riboflavin treatment as distinguishing features. From a retrospective study, relying mainly on metabolic data, we have identified a novel mutation, c.1067G > A (p.Gly356Glu) in exon 8 of ETFDH, in three South African Caucasian MADD patients with the index patient presenting the hallmark features of type I MADD and two patients with compound heterozygous (c.1067G > A + c.1448C > T) mutations presenting with MADD type III. SDS-PAGE western blot confirmed the significant effect of this mutation on ETFDH structural instability. The identification of this novel mutation in three families originating from the South African Afrikaner population is significant to direct screening and strategies for this disease, which amongst the organic acidemias routinely screened for, is relatively frequently observed in this population group.en© 2017 Elsevier B.V. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Journal of the Neurological Sciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Journal of the Neurological Sciences vol. 384, pp. 121-125, 2018. doi : 10.1016/j.jns.2017.11.012.Multiple acyl-CoA dehydrogenase deficiency (MADD)Glutaric aciduria type II (GAII)Metabolic disorderElectron transfer protein (ETF)Autosomal recessive disorderCongenital abnormalitiesRiboflavinOrganic acidemiasA novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiencyPostprint Article