Secondary Coenzyme Q10 Deficiencies

Dear Colleagues,

Secondary coenzyme Q10 (CoQ10) deficiencies result from mutations in genes that are not directly related to the CoQ10 biosynthetic pathway or to non-genetic factors. Secondary CoQ10 deficiencies have been associated with a number of disorders, including primary mitochondrial respiratory chain (MRC) disorder, cardiovascular disease, chronic kidney disease, type II diabetes and metabolic syndrome. Recently, evidence of a plasma CoQ10 deficiency was reported in the lysosomal storage disorder mucopolysaccharidosis (MPS), as well as the metabolic disease phenylketonuria (PKU). CoQ10 deficiency has also been associated with aberrant sulphide metabolism. Plasma CoQ10 status reflects both hepatic synthesis and dietary intake, and therefore it may not accurately represent the cellular level of this isoprenoid. However, evidence of a deficit in fibroblast CoQ10 status has been reported in MPS patients with Sanfilippo syndrome A and B (MPS III), although there was no detectable impairment in the CoQ10 biosynthetic pathway. In primary MRC disorders, an aberrant respiratory chain may affect the structural integrity or formation of the CoQ10 biosynthetic enzyme complex. This complex is located in the inner mitochondrial membrane close to the respiratory chain, and could therefore impair the synthesis of CoQ10. Evidence for secondary CoQ10 deficiencies have also been reported in association with HMG-CoA reductase inhibitors, `statins` and Amitriptyline therapy.

The factors responsible for inducing a deficit in CoQ10 status in secondary CoQ10 deficiencies are currently not well understood. In some cases these factors may be disease-specific, such as inhibition of the mevalonate pathway by high phenylalanine concentrations in PKU. Another example is the low blood levels of vitamin B₆ reported in MPS patients, with the active form of vitamin B₆, pyridoxal 5-phosphate, being an important cofactor for the CoQ10 biosynthetic pathway.

Degradation of CoQ10 induced by oxidative stress (OS) has been suggested as a possible contributory factor to the low levels of this isoprenoid reported in certain diseases, although this remains to be confirmed. OS could also inhibit enzymes in the CoQ10 biosynthetic pathway, which may in turn reduce the cellular CoQ10 status, although this putative mechanism has yet to be investigated. 

 When biochemical evidence of a CoQ₁₀ deficiency is detected, further studies are required to determine whether it is a primary or secondary CoQ₁₀ deficiency. Confirmation of the former requires diagnostic strategies using next generation sequencing, while the latter may require radiolabelled incorporation studies. Once diagnosed,  secondary CoQ10 deficiency may respond well to high dose oral CoQ₁₀ supplementation, although early diagnosis and treatment is essential to ensure an optimal clinical response.

The aim of this Special Issue is to present a selection of research articles and reviews that investigate the biochemical disease mechanisms responsible for secondary CoQ10 deficiencies, together with a description of appropriate diagnostic and  therapeutic strategies that target this condition.

Dr. Iain Hargreaves

Guest Editor

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