Mitochondrial diseases are a heterogeneous
group of disorders characterised by impaired mitochondrial
oxidative phosphorylation system. Most often for mitochondrial
disease, where no metabolic diagnostic biomarkers
exist, a deficiency is diagnosed after analysing the
respiratory chain enzymes (complexes I-IV) in affected
tissues or by identifying one of an ever expanding number
of DNA mutations. This presents a great challenge to
identify cases to undergo the invasive diagnostic procedures
required. An untargeted liquid chromatography mass
spectrometry metabolomics approach was used to search
for a metabolic biosignature that can distinguish respiratory
chain deficient (RCD) patients from clinical controls (CC).
A cohort of 37 ethnically diverse cases was used. Sample
preparation, liquid chromatography time-of-flight mass
spectrometry methods and data processing methods were
standardised. Furthermore the developed methodology
used reverse phase chromatography in conjunction with
positive electrospray ionisation and hydrophilic interaction
chromatography with negative electrospray ionisation.
Urine samples of 37 patients representing two different experimental groups were analysed. The two experimental
groups comprised of patients with confirmed RCDs and
CC. After a variety of data mining steps and statistical
analyses a list of 12 features were compiled with the ability
to distinguish between patients with RCDs and CC.
Although the features of the biosignature needs to be
identified and the biosignature validated, this study demonstrates
the value of untargeted metabolomics to identify
a metabolic biosignature to possibly be applied in the
selection criteria for RCDs.