Mitochondrial respiratory chain integrity depends on a number of proteins encoded by nuclear and mitochondrial genomes. Mutations of such factors can result in isolated or combined respiratory chain deficits, some of which can induce abnormal morphology of the mitochondrial network or accumulation of intermediary metabolites. Consequently, affected patients are clinically heterogeneous, presenting with central nervous system, muscular, or neurodegenerative disorders. ATAD3A is a nuclear-encoded ATPase protein of the AAA+ family and has been localized to the inner mitochondrial membrane. Recently reported mutations or large deletions in the ATDA3A gene in patients have been shown to induce altered mitochondrial structure and function and abnormal cholesterol metabolism in a recessive or dominant manner. Here, we report two siblings presenting axonal sensory-motor neuropathy associated with neonatal cataract. Genetic analyses identified two novel mutations in ATAD3A; a point mutation and an intronic 15 bp deletion affecting splicing and leading to exon skipping. Biochemical analysis in patient cells and tissues showed abnormal function of the mitochondrial respiratory chain in muscle and abnormal mitochondrial cristae structure. These new cases underline the large spectrum of biochemical and clinical presentations of ATAD3A deficiency and the different modes of inheritance, making it an atypical mitochondrial disorder.

线粒体呼吸链的完整性取决于核和线粒体基因组编码的许多蛋白质。此类因素的突变可导致孤立或合并的呼吸链缺陷，其中一些可诱导线粒体网络形态异常或中间代谢产物积聚。因此，受影响的患者在临床上是异质的，表现出中枢神经系统，肌肉或神经退行性疾病。ATAD3A是AAA +家族的核编码ATPase蛋白，已定位于线粒体内膜。最近报道的ATDA3A突变或大缺失事实证明，患者体内的这种基因以隐性或显性方式诱导线粒体结构和功能的改变以及胆固醇代谢异常。在这里，我们报告两个兄弟姐妹呈现与新生儿白内障相关的轴突感觉运动神经病。遗传分析确定了ATAD3A中的两个新突变; 点突变和内含子15 bp缺失会影响剪接并导致外显子跳跃。对患者细胞和组织进行的生化分析显示，肌肉中的线粒体呼吸链功能异常，线粒体的ista结构异常。这些新病例强调了ATAD3A缺乏的广泛生化和临床表现以及不同的遗传方式，使其成为非典型的线粒体疾病。