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Fourie 2015 Abstract MiPschool Cape Town 2015

From Bioblast
The association of Coenzyme Q10-deficiencies and respiratory chain disorders in South African patients.


Fourie J, Wilsenach K, Jonck LM, van der Westhuizen FH, Smuts I, Louw R (2015)

Event: MiPschool Cape Town 2015

Coenzyme Q10 (CoQ10), an essential component of the respiratory chain, shuttles electrons from complex I and II to complex III. CoQ10 deficiencies are therefore often associated with respiratory chain disorders. CoQ10 deficiencies are heterogeneous and affected patients have varying degrees of CoQ10 shortage. The aim of this study was to determine the association of defects in the biosynthesis of CoQ10 and associated respiratory chain deficiencies in South Africa patients. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was standardized in order to quantify CoQ10 in muscle samples, using a stable isotope dilution approach. The quantification of CoQ10 was then performed on muscle specimens of patients (n=155) that clinically qualified for electron transport chain analyses. Seventy nine were clinically referred controls and 76 had confirmed respiratory chain deficiencies of which 29 patients had CII+III deficiencies. Ion torrent next generation sequencing was performed on 24 patients including 9 patients with decreased as well as 15 patients with normal CoQ10 levels. Eighteen targeted genes involved in primary and secondary CoQ10 were sequenced. Eight patients, all with combined complex I&II deficiencies had deficient CoQ10 concentrations in muscle samples. Sixteen possible disease-causing variants were identified. Three compound heterozygous variants in three patients with low CoQ10 levels were found in the ETFDH, COQ6 and COQ7 genes respectively. Pathogenicity was proven in the ETFDH and COQ6 genes. To conclude, only mitochondrial patients with confirmed CII+III enzyme deficiencies had statistically significant low CoQ10 levels and at least two patients had pathogenic novel mutations in the ETFDH and COQ6 genes.

Labels: MiParea: Respiration, Instruments;methods, mtDNA;mt-genetics, mt-Medicine, Patients 

Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Skeletal muscle 

Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, TCA cycle and matrix dehydrogenases 



North-West Univ, Potchefstroom Campus, South Africa. - [email protected]