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

作者：van der Westhuizena Francois H^*; Smuts Izelle; Honey Engela; Louw Roan; Schoonen Maryke; Jonck Lindi Maryn; Dercksen Marli

来源：Journal of the Neurological Sciences, 2018, 384: 121-125.

DOI：10.1016/j.jns.2017.11.012

• Multiple acyl-CoA dehydrogenase deficiency
• MADD
• Glutaric aciduria type II
• ETFDH

Neonatal-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.Gly356G1u) 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.

• 出版日期2018-1-15
• 单位西北大学