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

Sainath Raman,Catherine Devile,Mark J Peters,Shamima Rahman,Latifa Chentouf,Manabu Sakakibara

doi:10.1371/journal.pone.0199756

Sainath Raman, Catherine Devile + Show 4 more

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https://doi.org/10.1371/journal.pone.0199756

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Abstract

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.

Highlights

Mitochondrial diseases (MD) are rare with an estimated birth prevalence of 1 in 5000 in the western world.[1]
A low ΔTOI identifies cases with a higher probability of mitochondrial disease or neurogenetic disease compared to healthy controls
Results for other Fagan nomogram comparisons are provided as supplemental information. (S3 Table)

Summary

Introduction

Mitochondrial diseases (MD) are rare with an estimated birth prevalence of 1 in 5000 in the western world.[1] In comparison, neurogenetic diseases (ND) are more common; a recent study estimated a prevalence of 1 in 1100 in Northern England.[2]. Both these groups of children frequently present in early childhood with delay in reaching developmental milestones, or an acute admission to the emergency department with lactic acidosis and/or a multi-system disorder.[3]. 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

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