Coenzyme Q10 deficiency

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

The first defect in coenzyme Q10 (ubiquinone) biosynthesis has been attributed to mutations in COQ2, encoding Para-Hydroxybenzoate-Polyprenyl Transferase. Patients with primary CoQ10 deficiency can present with myopathy, cerebellar involvement, generalized encephalopathy, and/or renal involvement. Analysis of respiratory chain enzyme activities reveal normal levels of the complexes taken individually, but low levels of complexes I+III and of complexes II+III. See article by Quinzii, C.

For more information on mitochondrial respiratory chain defects, see OMMBID Chapter 104.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

One Response to “Coenzyme Q10 deficiency”

  1. pcampeau


    Coenzyme Q10

    Coenzyme Q10 (CoQ10) (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone) is a fat-soluble quinone that contains a side chain of 10 isoprenoid units. CoQ10 functions to transfer electrons from complex I to complex III and from complex II to complex III. This compound may also stabilize the OXPHOS complexes within the inner membrane and serve as a potent antioxidant for oxygen free radicals,579-584 even at physiological concentrations.585 In humans, the highest concentrations of coenzyme Q are found in heart, liver, kidney, and pancreas.586 Studies using rat hepatocytes demonstrated that 25 percent to 30 percent of coenzyme Q is localized in the cell nucleus, 40 percent to 50 percent in the mitochondrion, 15 percent to 20 percent in microsomes, and 5 percent to 10 percent in the cytosol.587

    Plasma levels in children and adults are 0.79 ± 0.22 0x0003bcg/ml. Following a single 100 mg oral dose, peak plasma levels occur in approximately 5 to 10 h with a mean plasma level of about 1 0x0003bcg/ml.588 The plasma half-life is estimated at 33.9 ± 5.32 h and approximately 90 percent of the steady-state concentration can be achieved after 4 days of treatment. In our experience with administration of CoQ10 to children and adults, an oral dose of 4.3 mg/kg/day results in an increase in the plasma level to 3 to 4 0x0003bcg/ml. Oral doses of CoQ10 appear to be taken up by chylomicrons, deposited in the liver, and packaged into very-low-density lipoproteins.589 Excretion is primarily through the biliary tract.590 During chronic administration, approximately 62.5 percent of the orally administered CoQ10 can be recovered in the feces. To date, no side effects have been reported.

    CoQ10 has been reported to have a beneficial effect on the clinical manifestations of a number of OXPHOS diseases. Clinical and metabolic improvement with CoQ10 administration has been noted in various classes of OXPHOS disease.74,312,314,591-601 CoQ10 doses have ranged from 30 to 300 mg/day with no side effects. In MELAS, doses of 300 mg/day were required for optimal therapeutic effects.312,314 A trial of CoQ10 (60 mg/day), vitamin B6 (180 mg/day), and ferrous citrate (150 mg/day) in 27 Alzheimer disease patients, 2 of whom harbored a missense mutation in the amyloid 0x0003b2-protein at codon 717 (Val to Ile), was reported to result in an improvement of mental status.602,603 In a multicenter, double-blind study where the participants had chronic progressive external ophthalmoplegias from a variety of causes (i.e., only a subset had mtDNA deletions), a decrease inpost exercise lactate levels was observed in about 30 percent of individuals and intention tremor improved in about 10 percent of individuals with cerebellar signs.600 This study employed a relatively low dose of CoQ10 (2 mg/kg/day) which resulted in only modest increases in blood CoQ10 levels. Positive therapeutic effects have also been reported in patients with angina pectoris,604,605 congestive heart failure,423,426,427,604-612 Adriamycin cardiotoxicity,613-616 and cardiac arrhythmias.592 Symptoms such as sleep disturbances, leg paresthesias, leg edema, and palpitations are anecdotally reported to be improved with CoQ10 administration.243 In our treatment of OXPHOS diseases, we administer CoQ10 at a dose of 4.3 mg/kg/day for both pediatric and adult patients. Due to the complexities of CoQ10 absorption, particularly in pediatric groups, analysis of CoQ10 blood levels can be helpful in optimizing the dose. For children and adults who are unable to swallow the CoQ10, this hydrophobic compound can be dissolved in vegetable oil. Once this is done, the vegetable oil can be added to food (applesauce, cereal, etc.) to make it more palatable.

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