AOCCN2017

講演情報

Poster Presentation

[P1-142~216] Poster Presentation 1

2017年5月11日(木) 09:30 〜 16:00 Poster Room B (1F Argos F)

[P1-168] Function evaluation from the lymphoblasts derived from patients with late-onset multiple acyl-CoA dehydrogenase deficiency

Yung-Ting Kuo1, 2 (1.Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, 2.Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan)

[Introduction] Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive inherited disorder of fatty acid metabolism. Electron-transfer-flavoprotein dehydrogenase (ETFDH) gene encodes electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO) have been reported to be the major causes of MADD. We postulate that this MADD pedigree may result from defects of ETF-QO combined with general mitochondrial dysfunction.
[Methodology]The putative mutations were tested for segregation in the family and in control chromosomes by direct sequencing. The protocol was approved by the Ministry of Science and Technology of Taiwan and the Taipei Medical University–Joint Institutional Review Board (TMU-JIRB-N201506002). Following informed patient consent, 15 ml of whole blood was withdrawn and collected in an EDTA-containing tube. EB virus-transformed lymphoblastoid cell lines from all participants were performed by the Food Industry Research and Development Institute (Hsinchu, Taiwan). Muscle biopsy was done by open biopsy from left vastus lateralis.
[Results] To underlying the genotype-phenotype relevance of ETFDH variations in the pathogenesis of MADD, we establish the specific lymphoblastoid cells differentially overexpressed with c.92C>T, c.250G>A, or c.92C>T/c.250G>A ETFDH mutations. Riboflavin and/or Coenzyme Q10 supplement reduced oil droplet accumulation. The percentage of Nile Red positive cells were compared among wild type (WT), c.92C>T, c.250G>A, or c.92C>T/c.250G>A cells with treatment of different types of palmitic (C16:0) acid. Approximate 7.6%, 38.3%, and 55.7% ORO positive cells were counted in WT, carrier (C1) and index patient (P1) cells without fatty acid treatment, respectively.
[Conclusions] This demonstration of the genetic basis for MADD provides the molecular insight of ETFDH deficiency induced mitochondrial dysfunctions. Finally, the disease model can be an advantage for future such as drug screening and clinical management.