The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene
The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene
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DOI：
10.1093/brain/awm054
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发表时间：
2007-08-01
期刊：
影响因子：
14.5
通讯作者：
Horvath, Rita
中科院分区：
文献类型：
--
作者：
Gempel, Klaus;Topaloglu, Haluk;Horvath, Rita
辅酶Q10（CoQ10）缺乏症是一种具有异质性表型表现和遗传背景的常染色体隐性遗传疾病。我们描述了来自五个独立家族的七名患有辅酶Q10缺乏症的孤立性肌病表型的患者，这些患者的临床、组织学和生化表现非常相似。所有患者均表现为运动不耐受、乏力、近端肌病和高血清CK。肌肉组织学显示脂质积聚和线粒体肌病的细微体征。肌肉匀浆的生化测定显示呼吸链复合物I和II + III的活性严重降低，而复合物IV（考克斯）中度降低。辅酶Q10显着减少，在骨骼肌的所有patients.Tandem质谱检测到多个酰基辅酶A缺乏症，导致电子转移黄素蛋白脱氢酶（ETFDH）基因的分析，以前被证明会导致另一种代谢紊乱，谷氨酸尿症11型（GAII）。所有患者均携带ETFDH常染色体隐性突变，表明ETFDH缺乏导致继发性CoQ10缺乏。我们的研究结果表明，晚发型形式的GAII和肌病形式的辅酶Q10缺乏症是等位基因疾病。由于这种情况是可以治疗的，正确的诊断是至关重要的，应该考虑在儿童和成人。我们建议患者同时补充辅酶Q10和核黄素，特别是长期治疗。
Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency.The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients.Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type 11 (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.