A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options

Coenzyme Q(10) (CoQ(10)) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ(10) is synthesized by all cells and defects in the synthesis pathway result in primary CoQ(10) deficiency that frequently leads to severe mitochondrial disease syndrome. CoQ(10) is exceedingly hydrophobic, insoluble, and poorly bioavailable, with the result that dietary CoQ(10) supplementation produces no or only minimal relief for patients. We studied a patient from Turkey and identified and characterized a new mutation in the CoQ(10) biosynthetic gene COQ7 (c.161G > A; p.Arg54Gln). We find that unexpected neuromuscular pathology can accompany CoQ(10) deficiency caused by a COQ7 mutation. We also show that by-passing the need for COQ7 by providing the unnatural precursor 2,4-dihydroxybenzoic acid, as has been proposed, is unlikely to be an effective and safe therapeutic option. In contrast, we show for the first time in human patient cells that the respiratory defect resulting from CoQ(10) deficiency is rescued by providing CoQ(10) formulated with caspofungin (CF/CoQ). Caspofungin is a clinically approved intravenous fungicide whose surfactant properties lead to CoQ(10) micellization, complete water solubilization, and efficient uptake by cells and organs in animal studies. These findings reinforce the possibility of using CF/CoQ in the clinical treatment of CoQ(10)-deficient patients.