Near infrared spectroscopy with a vascular occlusion test as a biomarker in children with mitochondrial and other neuro-genetic disorders

BackgroundMitochondrial and neurogenetic diseases can present diagnostic challenges. We investigated if near infrared spectroscopy with the vascular occlusion test is able to differentiate between children with mitochondrial disease and children with neurogenetic disease or healthy controls.MethodsProspective observational study conducted in a tertiary children’s hospital.ResultsForty-three children with mitochondrial disease (including both genetically confirmed primary mitochondrial disease and cases with biochemical evidence of mitochondrial dysfunction), 19 children with non-mitochondrial neurogenetic disease and 13 healthy controls were recruited. The delta tissue oxygen index (ΔTOI) values showed greater variability amongst children with mitochondrial disease and neurogenetic disease than healthy controls despite the median ΔTOI being similar (median 14.1 and 18.8, t-test, p = 0.16). A low ΔTOI identifies cases with a higher probability of mitochondrial disease or neurogenetic disease compared to healthy controls (positive likelihood ratio: 3.67; 95%CI:1.01–13). A high ΔTOI with the near infrared spectroscopy with vascular occlusion test identifies cases with a lower probability of having a disease (negative likelihood ratio: 0.51; 95%CI:0.36–0.74).ConclusionNear infrared spectroscopy with vascular occlusion test might be able to discriminate children with mitochondrial disease and neurogenetic disease from healthy controls.背景 线粒体疾病与神经遗传性疾病的临床诊断均颇具挑战。本研究旨在探讨结合血管闭塞试验（vascular occlusion test）的近红外光谱（near infrared spectroscopy）技术，能否区分线粒体疾病患儿、非线粒体源性神经遗传性疾病患儿与健康对照人群。 方法 本研究为一项于三级儿童医院开展的前瞻性观察性研究。 结果 本研究共纳入43例线粒体疾病患儿（涵盖经基因确诊的原发性线粒体疾病，以及存在线粒体功能障碍生化证据的病例）、19例非线粒体源性神经遗传性疾病患儿，以及13名健康对照儿童。结果显示，尽管组织氧合指数差值（delta tissue oxygen index, ΔTOI）的中位数在三组间无显著差异（中位数分别为14.1与18.8，t检验，p=0.16），但线粒体疾病与神经遗传性疾病患儿的ΔTOI值变异程度显著高于健康对照儿童。当ΔTOI处于低水平时，相较于健康对照儿童，患儿罹患线粒体疾病或神经遗传性疾病的概率更高（阳性似然比（positive likelihood ratio）：3.67；95%CI：1.01–13）；而结合血管闭塞试验的近红外光谱检测若呈现高ΔTOI值，则提示患儿罹患疾病的概率相对更低（阴性似然比（negative likelihood ratio）：0.51；95%CI：0.36–0.74）。 结论 结合血管闭塞试验的近红外光谱技术，或可实现线粒体疾病患儿、神经遗传性疾病患儿与健康对照儿童的鉴别诊断。