Neurometabolic disorders stem from errors in metabolic processes yielding a neurological phenotype. A subset of those disorders encompasses mitochondrial abnormalities partially due to mitochondrial DNA (mtDNA) depletion. mtDNA depletion can be attributed to inheritance, spontaneous mutations or acquired from drug-related toxicities. In the armamentarium of diagnostic procedures, mtDNA quantification is a standard for disease classification. However, alterations in mtDNA obtained from peripheral tissues such as skin fibroblasts and blood cells do not often reflect the severity of the affected organ, in this case, the brain. The purpose of this review is to highlight the pitfalls of quantitating mtDNA from peripheral –and not limited to-tissues for diagnosing patients suffering from a variety of mtDNA depletion syndromes exhibiting neurologic abnormalities. In lieu, a qualitative test of mitochondrial substrate-level phosphorylation –even from peripheral tissues-reflecting the ability of mitochondria to rely on glutaminolysis in the presence of respiratory chain defects is proposed as a novel diagnostic assessment of mitochondrial functionality.

神经代谢紊乱源于代谢过程中产生神经表型的错误。这些疾病的一部分包括线粒体异常，部分是由于线粒体DNA（mtDNA）耗竭所致。mtDNA耗竭可归因于遗传，自发突变或从与药物相关的毒性中获得。在诊断程序的设备中，mtDNA定量是疾病分类的标准。但是，从周围组织（如皮肤成纤维细胞和血细胞）获得的mtDNA的变化通常不会反映出受影响器官（在这种情况下为大脑）的严重程度。这篇综述的目的是强调从外周定量mtDNA的陷阱-不仅限于组织，以诊断患有各种表现出神经系统异常的mtDNA消耗综合症的患者。取而代之的是，对线粒体底物水平的磷酸化进行定性测试，甚至从周围组织反映线粒体在呼吸链缺陷存在时依靠谷氨酰胺分解的能力，都可以作为线粒体功能性的新型诊断方法。