Demirbas Didem, Harris David J, Arn Pamela H, Huang Xiaoping, Waisbren Susan E, Anselm Irina, Lerner-Ellis Jordan P, Wong Lee-Jun, Levy Harvey L, Berry Gerard T
Division of Genetics and Genomics, Manton Center for Orphan Disease Research Boston Children's Hospital, Harvard Medical School Boston Massachusetts.
Department of Pediatrics Nemours Children's Health System Jacksonville Florida.
JIMD Rep. 2019 Mar 14;46(1):63-69. doi: 10.1002/jmd2.12018. eCollection 2019 Mar.
Succinyl-CoA synthetase or succinate-CoA ligase deficiency can result from biallelic mutations in gene that encodes for the alpha subunit of the succinyl-CoA synthetase. Mutations in this gene were initially associated with fatal infantile lactic acidosis. We describe an individual with a novel biallelic pathogenic mutation in with a less severe phenotype dominated by behavioral problems. The mutation was identified to be c.512A>G corresponding to a p.Asn171Ser change in the protein. The liquid chromatography tandem mass spectrometry-based enzyme activity assay on cultured fibroblasts revealed a markedly reduced activity of succinyl-CoA synthetase enzyme when both ATP and GTP were substrates, affecting both ADP-forming and GDP-forming functions of the enzyme.
琥珀酰辅酶A合成酶或琥珀酸辅酶A连接酶缺乏症可能由编码琥珀酰辅酶A合成酶α亚基的基因双等位基因突变引起。该基因的突变最初与致命性婴儿乳酸酸中毒有关。我们描述了一名个体，其该基因存在一种新的双等位基因致病性突变，具有以行为问题为主的较轻表型。该突变被鉴定为c.512A>G，对应于蛋白质中的p.Asn171Ser变化。基于液相色谱串联质谱的培养成纤维细胞酶活性测定显示，当ATP和GTP均为底物时，琥珀酰辅酶A合成酶的活性显著降低，影响了该酶的ADP形成和GDP形成功能。
