Schrank Bertold, Schoser Benedikt, Klopstock Thomas, Schneiderat Peter, Horvath Rita, Abicht Angela, Holinski-Feder Elke, Augustis Sarunas
Department of Neurology, DKD HELIOS Medical Center Wiesbaden, Wiesbaden, Germany.
Friedrich-Baur-Institute, Department of Neurology, University Hospital of LMU Munich, Munich, Germany.
Neuromuscul Disord. 2017 May;27(5):473-476. doi: 10.1016/j.nmd.2017.02.005. Epub 2017 Feb 14.
We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9.
我们报告了一名36岁女性，她终生存在运动不耐受、乳酸酸中毒并伴有恶心，伴有新发现的复合杂合型酰基辅酶A脱氢酶9基因（ACAD9）突变（p.Ala390Thr和p.Arg518Cys）。ACAD9是线粒体呼吸链复合体I的组装因子。ACAD9突变被认为是复合体I缺乏的常见原因。我们的患者自幼年起就出现运动不耐受、快速疲劳和恶心。轻度体力活动会反复引发恶心和呕吐。她的神经系统检查、实验室检查结果和肌肉活检均未发现异常。自行车运动心肺功能测试在运动期间和运动后引发了明显的乳酸酸中毒，提示存在线粒体疾病。随后，对肌肉中呼吸链酶活性的分析显示严重的孤立性复合体I缺乏。候选基因测序发现了两个新的杂合型ACAD9突变。本病例报告扩展了与ACAD9突变相关疾病的突变和表型谱。
