Abstract：
Clinical variability and substantial overlap between mitochondrial disorders and other genetic disorders and inborn errors make the clinical and metabolic diagnosis of mitochondrial disorders quite challenging. Evaluating specific laboratory markers is essential in the diagnostic process, but mitochondrial disease can be present in the absence of any abnormal metabolic markers. In this chapter, we share the current consensus guidelines for metabolic investigations, including investigations in blood, urine, and the cerebral spinal fluid and discuss different diagnostic approaches. As personal experience might significantly vary and there are different recommendations published as diagnostic guidelines, the Mitochondrial Medicine Society developed a consensus approach based on literature review for metabolic diagnostics in a suspected mitochondrial disease. According to the guidelines, the work-up should include the assessment of complete blood count, creatine phosphokinase, transaminases, albumin, postprandial lactate and pyruvate (lactate/pyruvate ratio when the lactate level is elevated), uric acid, thymidine, amino acids, acylcarnitines in blood, and urinary organic acids (especially screening for 3-methylglutaconic acid). Urine amino acid analysis is recommended in mitochondrial tubulopathies. CSF metabolite analysis (lactate, pyruvate, amino acids, and 5-methyltetrahydrofolate) should be included in the presence of central nervous system disease. We also suggest a diagnostic strategy based on the mitochondrial disease criteria (MDC) scoring system in mitochondrial disease diagnostics; evaluating muscle-, neurologic-, and multisystem involvement, and the presence of metabolic markers and abnormal imaging. The consensus guideline encourages a primary genetic approach in diagnostics and only suggests a more invasive diagnostic approach with tissue biopsies (histology, OXPHOS measurements, etc.) after nonconclusive genetic testing.
摘要：
线粒体疾病与其他遗传性疾病和先天性错误之间的临床变异性和大量重叠使得线粒体疾病的临床和代谢诊断相当具有挑战性。评估特定的实验室标志物在诊断过程中至关重要，但是线粒体疾病可以在没有任何异常代谢标记的情况下存在。在这一章中,我们分享目前关于代谢研究的共识指南，包括血液调查，尿液,和脑脊液，并讨论不同的诊断方法。由于个人经验可能会有很大差异，并且有不同的建议作为诊断指南发布，线粒体医学会在文献综述的基础上,针对疑似线粒体疾病的代谢诊断制定了共识方法.根据指导方针,工作应包括评估全血细胞计数，肌酸磷酸激酶，转氨酶，白蛋白,餐后乳酸和丙酮酸（当乳酸水平升高时，乳酸/丙酮酸比率），尿酸,胸苷,氨基酸,血液中的酰基肉碱,和尿有机酸（特别是3-甲基戊二酸的筛选）。建议在线粒体肾小管疾病中进行尿液氨基酸分析。CSF代谢物分析(乳酸，丙酮酸,氨基酸,和5-甲基四氢叶酸）应包括在存在中枢神经系统疾病的情况下。我们还建议在线粒体疾病诊断中基于线粒体疾病标准（MDC）评分系统的诊断策略;评估肌肉-，神经学-，和多系统参与，代谢标志物和异常成像的存在。共识指南鼓励在诊断中采用主要的遗传学方法，并且仅建议采用更具侵入性的组织活检诊断方法（组织学，OXPHOS测量,等。)在非结论性基因测试后。
